[1] Lucas returned to his law practice following his military service and served as a state's attorney for Mason County from 1920 to 1925.

[6] In 1932, he was defeated by William H. Dieterich for the Democratic nomination to challenge Republican incumbent Otis F. Glenn for a United States Senate seat from Illinois.

"[3] In 1938, after William Dieterich declined to run for re-election, Lucas was elected to the U.S. Senate over Republican Richard J. Lyons, with a 51%–48% victory.

[citation needed] Lucas was a favorite son candidate and among twelve nominated at the 1944 Democratic National Convention to serve as Franklin D. Roosevelt's running mate in the presidential election that year.

However, he was unable to build a consensus as Senate Majority Leader with the onset of the anticommunist era, and lost in 1950, to Republican Everett Dirksen.

Overall, as Congressman and Senator Lucas focused on civil rights, labor unions, foreign policy, and agriculture.

He supported Franklin Roosevelt's main foreign policy initiatives, including Lend-Lease in 1941 for military aid to the Allies, and the creation of the United Nations.

Lucas supported the New Deal farm programs, which were popular in rural Illinois, especially the Agricultural Adjustment Act of 1938.