During the 1920s, Mikawa served as chief navigator on a number of ships, including the Haruna, Tatsuta, Ikoma, and Aso. He was subsequently an instructor at the Naval Torpedo School and held several other highly-visible posts. At the end of the decade, Commander Mikawa was part of the delegation to the London Naval Conference and shortly thereafter became naval attaché in Paris. Promoted to the rank of captain in late 1930, he returned to Japan to take up administrative and training duties.
From 1 December 1936 to 15 November 1937 he was chief of staff of the IJN 2nd Fleet. Mikawa had duty with the Imperial Japanese Navy General Staff and Imperial General Headquarters from 1937 -1939, then went to sea again to command a succession of fleet squadrons, first in cruisers and then in battleships. He was promoted to vice admiral on 15 November 1940.
From 14 July 1942 until 1 April 1943 Mikawa commanded the newly formed IJN 8th Fleet in the South Pacific, based primarily at the major bases at Rabaul on New Britain and Kavieng on New Ireland. During that time, he led Japanese naval forces involved in the Guadalcanal and Solomon Islands campaigns. On August 8 - 9, 1942 he led a force of cruisers that defeated Allied naval forces in the Battle of Savo Island. However, Mikawa was sharply criticized for his failure to aggressively follow up on his victory, withdrawing before he could sink the lightly defended Allied transports.
On the night of November 13 – 14, 1942 Mikawa led a cruiser force that bombarded Henderson Field on Guadalcanal during the Naval Battle of Guadalcanal. Throughout the Guadalcanal campaign he often directed runs of the “Tokyo Express” that delivered men and materiel to Guadalcanal. However, his attempt to land Japanese reinforcements in Lae turned into the disastrous Battle of the Bismark Sea, and he eventually had to take responsibility for the loss of the Solomon Islands, and was re-assigned to rear areas, such as the Philippines.
Mikawa had Naval General Staff and other shore posts in Japan during April-September 1943. From 3 September 194 to 18 June 1944 he commanded the 2nd Southern Expeditionary Fleet in the Philippines. Afterwards, he commanded the Southwestern Area Fleet and 13th Air Fleet from 18 June to 1 November 1944, also in the Philippines. Reassigned to Japan following the October, 1944 Battle of Leyte Gulf, he left active duty in May, 1945.