Lemke was the attorney general of North Dakota from 1921 to 1922. He later was elected to the United States House of Representatives in 1932, as a part of the Nonpartisan League. He served four two-year terms in Congress. While in Congress, Lemke earned a reputation as a progressive populist and supporter of the New Deal, championing the causes of family farmers and co-sponsoring legislation to protect farmers against foreclosures during the Great Depression.

In 1934, Lemke co-sponsored the Frazier-Lemke Farm Bankruptcy Act, restricting the ability of banks to repossess farms. President Franklin D. Roosevelt signed the act into law on June 28, 1934.

Later in 1936, Lemke accepted the nomination of the Union Party, a short-lived third party, as their candidate for President of the United States. He received 892,378 votes, or just under 2% nationwide, and no electoral votes in the 1936 election. Simultaneously, he was reelected to the House of Representatives as a Republican.

In 1940, after having already received the Republican nomination for a fifth House term, he withdrew from that race to launch an unsuccessful run as an independent for the U.S. Senate. He ran again for Congress in 1942 as a Republican and served four more terms, until his death in 1950.