Early in January 1938, Vincennes was assigned to Cruiser Division 7, Scouting Force, and steamed through the Panama Canal to San Diego, California. In March, the ship participated in Fleet Problem XIX in the Hawaiian area before returning to San Pedro, California for operations off the west coast for the remainder of the year.
Following an overhaul at the Mare Island Navy Yard which lasted through April 1939, the cruiser returned east, transited the Panama Canal on 6 June in company with , , and and anchored in Hampton Roads on the 13th. For the next two months, she operated out of Norfolk in the vicinity of the Chesapeake lightship and the southern drill grounds. On 1 September 1939—the day on which Hitler's legions marched into Poland and commenced hostilities in Europe—Vincennes lay at anchor off Tompkinsville, New York. She then began conducting Neutrality Patrols off the east coast, ranging into the Caribbean Sea and the Gulf of Yucatan, and continued these duties through the spring of 1940.
Late in May, as German troops were smashing Allied defenses in France, Vincennes steamed to the Azores and visited Ponta Delgada from 4 June to 6 June 1940 before she proceeded on for French Morocco to load a shipment of gold for transport to the United States. While at anchor at Casablanca, the ship received word of Italy's declaration of war upon France—the "stab in the back" condemned by President Roosevelt soon thereafter. Vincennes' commanding officer, Capt. J. R. Beardall (later to become Naval Aide to the President) noted subsequently in his official report of the cruise that "it was apparent that the French bitterly resented this [the declaration of war] and despised Italy for her actions." After departing North African waters on 10 June, the cruiser returned to the United States to offload her precious metallic cargo and return to the drudgery of Neutrality Patrols.
Vincennes joined other Fleet units for landing exercises at Culebra, Puerto Rico, on 4 February 1941 and sent her 50-foot boats to assist in unloading and troop debarkation drills. She assisted transports and in landing men and material before taking station with Fire Support Group II. The cruiser then fired simulated gunfire support operations with her main and secondary batteries in exercises which foreshadowed her future combat role in the South Pacific.
For the remainder of February, the ship continued her landing support operations with Transport Divisions 2 and 7, anchoring on occasion at Mayagüez or Guayanilla, Puerto Rico. Conducting operations out of Puerto Rican waters, Vincennes called at Pernambuco, Brazil, on 17 March and got underway for Cape Town, South Africa, on the 20th. Arriving to a warm welcome nine days later, the ship took on a large shipment of gold bullion to pay for arms purchased in the United States by the United Kingdom and then headed home on the 30th. En route to New York, she conducted exercises. After a brief post-voyage period of repairs, the heavy cruiser sailed for the Virginia Capes, where she rendezvoused with and ; proceeded on to Bermuda; and dropped anchor in Grassy Bay on 30 April. She patrolled in the Caribbean and off the Atlantic coast of the United States through June.
After continuing her duties with the Neutrality Patrol into the autumn as American naval forces in the North Atlantic found themselves engaged in a de facto war with Germany, Vincennes undertook another mission to South African waters. She left the east coast late in November with Convoy WS-12, American transports carrying British troops. On 7 December 1941, the cruiser fought its way through heavy seas. Walls of water mercilessly pounded the ships of the convoy; and waves battered Vincennes, smashing a motor whaleboat to pieces and ripping a Curtiss SOC Seagull floatplane from its "moorings" on the storm-lashed well-deck amidships. The plane was battered against the catapult silos and into the hangar doors before it was swept over the ship's side. By that evening, however, the ship learned that she was not only at war with the elements but with Japan as well. Japanese naval air forces had struck Pearl Harbor and plunged the United States into war.
The heavy cruiser—now a part of Task Force 18, built around Hornet—departed San Francisco on 2 April. The carrier bore a strange deck cargo, 16 Army B-25 medium bombers slated to strike at Japan's heart. Vincennes rendezvoused with TF 16, built around and, with the combined might of the two task forces, struck out westward across the Pacific, headed toward Japanese home waters.
On the morning of 18 April, when the American warships were still some 150 miles from the planned launch point, an unexpected hitch developed. Japanese trawlers sighted and reported the task force. Vice Admiral William Halsey decided to fly off the bombers immediately. Accordingly, all 16 of the heavily loaded B-25s—laden with bombs and extra fuel—rose from Hornet's spray-slicked flight deck and climbed unsteadily into the leaden gray skies. Although the raid inflicted only minimal materiel damage upon the Japanese homeland, it nevertheless packed a powerful morale building "punch". When queried as to the base from whence the bombers had come, President Roosevelt said "from Shangri-La".
The combined Enterprise and Hornet task force retired eastward and made Pearl Harbor on 25 April. Departing again five days later, the ships, still screened by Vincennes, bent on speed toward the Coral Sea. However, they were too late to take part in the Battle of the Coral Sea.Vincennes' task force returned to Pearl Harbor on 26 May but got underway again on the 29th, bound for waters off Midway Island, which—according to American intelligence reports—a Japanese invasion force was approaching. By 4 June, the heavy cruiser and her sister ship , were steaming north of Midway.
At 16:40, after American air attacks had crippled three of the four Japanese carriers, a group of torpedo planes—"Kates"—from Japanese carrier Hiryū approached from the north. TF 17's radar soon picked them up when 15 miles out, and Yorktown launched planes to intercept as her screen deployed to bring an optimum concentration of antiaircraft fire to bear upon the approaching enemy. Three minutes after the first plane was spotted, combat air patrol F4F Wildcats from the carrier hit a Kate. The Japanese torpedo plane spiraled from the sky trailing a long streamer of smoke before crashing into the sea.
Vincennes opened fire at 16:44 with her 5 inch (127 mm), 20 mm, and 1.1 inch (28 mm) antiaircraft batteries on the Kates approaching from the port side. Increasing her speed to 25 knots and slowly turning to starboard, Vincennes kept her port guns trained on the enemy. While combing torpedo tracks, Vincennes hit a Kate and it went into the sea 150 yards (150 m) off her port bow.
The sharp, bitter action ended as quickly as it had begun. The Japanese had been driven off, but at a high cost for the Americans. Yorktown, mortally hit and listing to port, slowed to a halt, with smoke billowing from her wounded vitals. Vincennes altered course to follow Astoria's movements around the carrier, screening the stricken warship from further air attacks. However, on 6 June, Japanese submarine I-168 slipped through a screen of six destroyers and torpedoed Yorktown and destroyer , sinking the latter. The carrier went down early on the 7th.
Returning to Pearl Harbor, Vincennes entered the navy yard for repairs and alterations which lasted until early July. She then conducted tactical exercises off the island of Hawaii with other ships of TF 11 before departing Hawaiian waters on 14 July to rendezvous with TF 16, TF 18, and TF 62.Guadalcanal landings, Vincennes, in company with and Quincy, joined TF 62 on 26 July. On the 27th, the cruiser conducted approach exercises for landing practice and simulated bombardment drills off Koro Island in the Fiji group. As flagship for Task Group 62.3, Vincennes remained on station in the covering force in the transport area before undertaking further approach and landing exercise support drills.
Following refueling and revictualing, the heavy cruiser formed up with the American armada making its way to the Solomons. Vincennes, screening transport division "Yoke", arrived off Guadalcanal on 7 August. At daybreak, beneath overcast skies, the ship catapulted her spotting planes and then unlimbered her main and secondary batteries to commence shore bombardment. While the thunder of the supporting ships' gunfire reverberated across the waters, marines disembarked from their landing craft and stormed ashore to meet initially light resistance on the island.
Shortly after 13:20, Japanese planes launched a counterstrike. To sunward of the transports, Vincennes found herself in a favorable position to combat the attack and tracked the opposing planes—being among the first ships to open fire on the attackers. Forced to jettison their deadly loads prematurely, the Japanese retired without doing any damage, but not before Vincennes had bagged two of them. After sunset, Vincennes, Quincy, and Astoria—in company with and —retired to conduct screening patrols.
Returning to her covering duties at daylight, Vincennes arrived at transport area "X-ray", off Guadalcanal by daybreak. Two minutes before noon, Japanese bombers, intent on avenging their losses of the day before and disrupting the American landing, swooped down from Rabaul. Twenty-seven Mitsubishi G4M "Betty" bombers swept in, in a low-level torpedo attack and ran a gauntlet of gunfire from the transports and their escorting cruisers and destroyers. Three thousand yards (3 km) from the transports, Vincennes, as in the previous day's action, was again in favorable firing position and opened up with every gun in her battery, from 8 inch (203 mm) to 20 mm, that could bear on the attackers.
During the ensuing melee, the cruiser used her main-battery, 8 inch (203 mm) guns effectively, helping to down at least seven "Betties" which flew at an altitude of only 25 to 50 feet (7 to 15 m). The shell splashes from the main battery caused Japanese pilots to fly into walls of water or forced them to drastically alter their approaches. Vincennes dodged one torpedo which passed beneath her stern and evaded a bomb which fell off her port quarter. Unluckily, Jarvis, adjacent to the cruiser, took one torpedo hit which ultimately proved fatal to the ship.
Later, during the afternoon hours, aerial reconnaissance reported a Japanese surface force coming down from the base at Rabaul. These flights noted what was thought to be three Japanese cruisers, three destroyers and two gunboats or seaplane tenders steaming south. While Jarvis limped away from Lunga Point, Vincennes and her sisters Quincy and Astoria steamed, as the northern escort force, to a position off Savo Island to screen the vulnerable transports which were still unloading off the invasion beaches. Captain Frederick Lois Riefkohl of Vincennes assumed that the enemy ships reportedly en route from Rabaul were going to launch and support another air attack early the following morning. He accordingly shaped night orders to be especially vigilant during the midwatch and fully expected an air attack at daybreak.
Nearly an hour later, at about 01:45, lookouts spotted flares and star shell to the southward, accompanied by the low rumble of gunfire. The sound of the general quarters alarm soon rang throughout the ship and stirred her to action. Vincennes' lookouts were seeing the elimination of the southern escort group, based around Australian heavy cruiser Canberra and . Unbeknownst to the men manning the ships to the northward, a powerful enemy force was heading in their direction. Six cruisers and one destroyer under the command of Japanese Vice Admiral Gunichi Mikawa had turned north and were steaming directly towards Vincennes and her two sisters.
The first Japanese searchlight beams picked out Vincennes' splotchy camouflage shortly after 01:55, and the American cruiser opened fire with her main battery turrets to shoot out the troublesome light. Within a minute, however, Japanese shells bracketed the ship and Vincennes shuddered under the impact of the hail of steel screaming in from the ebony sky. Bridge, carpenter shop, "battle II", and radio antenna trunks all were hit in the first salvo.
Altering course to port, Riefkohl — who had leapt to the bridge at the alarm — rang down for increased speed; but, in the deafening din of battle, and with his ship and internal communications disrupted, it is doubtful that the order was received. Still moving at 19.5 knots, the heavy cruiser reeled under the impact of another group of direct hits.
Some of the shells in this group set afire the volatile planes in Vincennes' hangar space, and the resultant flames defied all attempts to put them out. A direct hit knocked the after antiaircraft director overboard. At 02:00, Vincennes heeled to starboard in an attempt to evade the accurate enemy fire, but the probing Japanese gunners were not about to let the already sorely wounded ship escape. One or two "Long Lance" torpedoes then ripped into the ship's number 1 fireroom and put it out of action.
Losing steering control five minutes later, Vincennes was dead in the water within minutes. Rapidly hitting shells quickly reduced the ship's gunpower to a fraction of its original strength and before long, snuffed it out entirely. Like a pummeled and reeling challenger in the boxing ring, Vincennes wallowed to a halt. Hit at least 57 times by 8- and 5 inch shells, the ship gradually assumed a more alarming list.
As if mercifully, at 02:10, the Japanese ceased fire and retired, leaving Savo Island and the burning hulks of the three American cruisers of the northern force in their wakes. As Vincennes' list increased to port, Riefkohl circulated the command to abandon ship at 02:30. Serviceable life jackets and rafts were broken out, and the crew began abandoning ship. At 02:40, the captain went down to the main deck and joined the last men to leave the sinking cruiser and jumped into the tepid waters of what would come to be known as Ironbottom Sound.
Riefkohl subsequently wrote a fitting epitaph: "The magnificent Vincennes, which we were all so proud of, and which I had the honor to command since 23 April 1941, rolled over and then sank at about 02:50, 9 August 1942, about 2½ miles east of Savo Island ... Solomons Group, in some 500 fathoms [910 m] of water."