Lemke was the attorney general of North Dakota from 1921 to 1922. He later was elected to the U.S. Congress in 1932 on the Republican Party ticket. He served four two-year terms in congress. In 1942, after an unsuccessful run as an independent for the U.S. Senate he ran again for Congress as a Republican and served four more terms, until his death in 1950.
In 1936 William Lemke accepted the nomination of the Union Party, a short-lived third party, as their candidate for President of the United States. He received 892,267 votes, or just under 2% nationwide, and no electoral votes. (see also: U.S. presidential election, 1936)
While in Congress, he 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 1936, he sponsored the Fraizer-Lemke Act, which would have provided for government refinancing of farm mortgages. President Franklin D. Roosevelt refused to support Lemke on that issue and ultimately sank the bill. Many believe Lemke's acceptance of the Union Party nomination in 1936 was out of bitterness toward Roosevelt over this issue.