Before running for lieutenant governor in 2010, Treadwell's involvement in political campaigning had been limited to his experiences as a state chair for Mitt Romney's 2008 presidential primary campaign and delegate to the Republican National Convention in 2008. In his first bid for public office, Treadwell won the Republican nomination for lieutenant governor of Alaska on August 24, 2010. He went on to win the 2010 midterm general election over Democratic nominee Diane E. Benson. Along with Governor Sean Parnell (R), Treadwell was sworn in on December 6, 2010.

Treadwell served as chair of the U.S. Arctic Research Commission from 2006 to 2010.

In his resignation letter to President Obama (D), Treadwell cited frustration with government spending and disappointment that Washington had not moved in recommendation from the Arctic Research Committee to address environmental issues.