Clark moved to Missouri in 1876 and settled at Bowling Green. He was successively a country newspaper editor, city attorney, county prosecuting attorney, and Missouri state legislator, and he served in the U.S. House of Representatives for 13 terms (1893–95, 1897–1921).

A follower of Democratic and Populist leader William Jennings Bryan, Clark consistently supported legislation favoured by Western and Southern agrarians. As a member of the Rules Committee and Democratic floor leader, he revolted against Speaker Joseph G. Cannon's dictatorial control over the House in 1910. His reminiscences, My Quarter Century of American Politics, were published in 1920.