He served in a variety of governmental posts in Illinois before he was first elected to the United States House of Representatives in 1934, and was elected senator in 1938. He was re-elected in 1944. With support from Harry Truman, he was elected party whip in 1946. Lucas, a moderate, drew support from conservative and liberal wings of the party. He took over the midwest campaign for President Truman and was credited with assisting not only Truman's 1948 reelection but bringing nine Democrats into the Senate. When Alben Barkley became vice-president and resigned his Senate seat, Lucas became majority leader. However, he was unable to build a consensus as Senate majority leader with the onset of the anti-Communist era, and lost re-election in 1950 to Republican Everett Dirksen. Lucas had become a target of Republican wrath with loss of political power in the Senate and the White House. His 1950 reelection campaign featured the active intervention into Illinois politics of Wisconsin Senator Joseph McCarthy who traveled the state with Rep. Dirksen saying that Senator Lucas was "soft on communism". The smear campaign led to a narrow victory for Dirksen.
He was succeeded as Democratic leader by Ernest McFarland, who also lost his reelection bid two years after assuming the leadership. The McCarthy intervention into other Senate campaigns was a factor in alienating his colleagues and his censure in 1954. Thanks to McFarland's successor, Lyndon Johnson, the Senate Democratic leadership became much more consolidated and more powerful.