In 1910 he narrowly won the Democratic primary for the United States Congress from the state's 3rd Congressional District, which was tantamount to election. Byrnes proved a brilliant legislator, working behind the scenes to form coalitions and avoiding the high-profile oratory that characterized much of Southern politics. He was a champion of the "good roads" movement that attracted motorists, and politicians, to large-scale road building programs in the 1920s. He became a close ally to President Woodrow Wilson, and Wilson often entrusted important political tasks to the capable young Congressman, rather than turning to more experienced lawmakers on Capitol Hill. Byrnes was also a protege of "Pitchfork" Ben Tillman, and often had a moderating influence on the fiery segregationist Senator.
Thanks largely to the opposition of his candidacy by the Ku Klux Klan, Byrnes lost the 1924 Senate primary to Coleman L. Blease, often considered a notorious demagogue. Out of office, he moved his law practice to Spartanburg, in the industrializing Piedmont region. Between his law practice and investment advice from friends such as Bernard Baruch, Byrnes became a wealthy man, but he never took his eyes off of a return to politics. He used his new base to gain the support of factory workers, and defeated Blease in 1930.
He had long been friends with Franklin D. Roosevelt, whom he supported for the Democratic nomination in 1932, and made himself the President's spokesman on the Senate floor, where he guided much of the early New Deal legislation to passage. He won easy reelection in 1936, promising:
"I admit I am a New Dealer, and if [the New Deal] takes money from the few who have controlled the country and gives it back to the average man, I am going to Washington to help the President work for the people of South Carolina and the country."
Since the colonial era, South Carolina's politicians had dreamed of an inland waterway system that would not only aid commerce, but also control flooding. By the 1930s, Byrnes took up the cause for a massive dam building project, the Santee Cooper, that would not only accomplish those tasks, but also electrify the entire state with hydroelectric power. With South Carolina financially strapped by the Great Depression, Senator Byrnes managed to get the Federal government to pay for the entire project, which was completed and put into operation in February of 1942.
In 1937 he supported Roosevelt on the highly controversial court packing plan, but voted against the minimum wage law of 1938 that would have made, as he argued, the textile mills in his state uncompetitive. He opposed Roosevelt's efforts to purge conservative Democrats in the 1938 primary elections. On foreign policy, however, he was a champion of Roosevelt's positions of helping Great Britain and France against Germany in 1939-41, and of maintaining a hard diplomatic line against Japan.
In part as a reward for his crucial support on many issues, Byrnes was named as an Associate Justice of the Supreme Court by FDR in 1940, a role which quickly bored him at a time when the country was about to go to war. He only served in that position for a year and a half from 1941 to 1942, whereupon he resigned in order to serve Roosevelt in a new, and in many ways unprecedented, capacity.
He was a serious possibility for vice president in 1944. However, he was too conservative for the labor unions, big city bosses vetoed any ex-Catholic, and blacks were wary of his opposition to racial integration. The nomination went to Senator Harry S. Truman. Roosevelt brought Byrnes to the Yalta Conference in early 1945, where he seemed to favor Soviet plans. Writing in shorthand, his notes comprise one of the most complete records of the "Big Three" Yalta meetings.
Upon his succession to the presidency after Roosevelt's death on April 12, 1945, Truman relied heavily on Byrnes's counsel, he (Byrnes) having been a mentor to Truman from Truman's earliest days in the U.S. Senate. One of the first people whom Truman saw on the following day was Byrnes, who shared information with the new President on the atomic bomb project (Truman had known nothing about the Manhattan Project beforehand). When Truman met Roosevelt's coffin in Washington, he asked Byrnes and former vice-president Henry A. Wallace, the two other men who might well have been FDR's successor, to join him at the train station, and he intended for them to play leading roles in his administration as a sign of continuity with Roosevelt's policies; while Truman quickly fell out with Wallace, he began turning more and more to Byrnes for support.
Truman appointed him as Secretary of State on July 3, 1945. He played a major role at the Potsdam Conference, the Paris Peace Conference, and other major postwar conferences. According to historian Robert H. Ferrell, Byrnes knew little more about foreign relations than Truman. He made decisions after consulting a few advisors, such as Donald S. Russell and Benjamin V. Cohen, and Byrnes and his small group paid little attention to the department and similarly ignored the president.
In 1946 he took an increasingly hardline position in opposition to Stalin, culminating in the speech held in Stuttgart September 6, 1946. "Restatement of Policy on Germany", also known as the "Speech of hope" it set the tone of future U.S. policy as it repudiated the Morgenthau Plan economic policies and gave the Germans hope for the future. Byrnes was named TIME magazine's Person of the Year. Although his tough position against the Soviets paralleled the feelings of the President, personal relations between the two men grew strained, particularly when Truman felt that Byrnes was attempting to set foreign policy by himself, and only informing the President afterward; Truman and others believed that Byrnes had grown resentful that he had not been FDR's running mate and Oval Office successor, and in his resentment he was disrespecting Truman. Whether this was true or not, Byrnes felt compelled to resign from the Cabinet in 1947 with some feelings of bitterness.
Ironically, Byrnes was initially seen as a strong progressive voice for moderate Negro rights. Recognizing that the South could not continue with its entrenched segregationist policies much longer, but fearful of Congress imposing sweeping civil rights upon the South, he opted for a course of change from within. To that end, he sought to at last fulfill the Supreme Court's promise of "separate but equal," particularly in regard to public education, and he poured state money into improving Negro schools, buying new textbooks and new buses, and hiring additional teachers. He also sought to curb the power of the Ku Klux Klan by passing a law that prohibited adults from wearing a mask in public on any day other than Halloween; by this measure, he knew that many Klansmen feared exposure, and would not appear in public in their robes unless their faces were hidden as well. Byrnes hoped to make South Carolina an example for other Southern states to modify their "Jim Crow" policies. That didn't stop the NAACP from filing a suit against South Carolina to force the state to desegregate its schools. Byrnes turned to Kansas, a Northern state which also segregated its schools, to provide a "friend of the court" statement supporting the right of school segregation on his state's behalf in the trial. This gave the NAACP's lawyer, Thurgood Marshall, the idea to shift the suit from South Carolina over to Kansas, which led directly to Brown v. Board of Education.
The South Carolina state constitution limited governors to one four-year term, and Byrnes retired from active political life following the 1954 election.
In his later years, Byrnes foresaw the South as a much more important player in national politics, and to hasten that development, he sought to end the South's automatic support of the Democratic Party (which Byrnes felt had grown too liberal, and which took the "Solid South" for granted at election time, yet otherwise ignored the region and its needs), and to realign it with the Republican Party. This was despite the fact that Byrnes remained a registered Democrat for much of the rest of his life.
Byrnes endorsed Dwight D. Eisenhower in 1952 and 1956, Richard Nixon in 1960 and 1968 and Barry Goldwater in 1964. He gave his private blessing to South Carolina Senator Strom Thurmond to bolt the Democratic Party in '64 and declare himself a Republican, but Byrnes himself remained a registered Democrat that year. He eventually switched formal allegiances to the Republican Party. In 1968, he secretly advised Nixon on how to win over old-time Southern Democrats to the Republican Party.