Whaley was first elected to the Dayton City Commission in 2005, Nan was one of the youngest women ever chosen for a commission seat. Nan served on the Montgomery County Board of Elections and as a deputy to Montgomery County Auditor Karl Keith. Whaley was elected mayor of Dayton in 2013, winning 56 percent of the vote. In 2017, she was unopposed for reelection, making it the first uncontested mayoral race in the city’s history since voters have elected the office separately. Before her election as Mayor she served on Greater Ohio’s Community Revitalization Committee, the Learn to Earn Executive Committee for Education, the Montgomery County Planning Commission and the Dayton Access Television Board of Trustees.

Early in her political career Whaley, while in college, was instrumental in reorganizing the College Democrats and later served as Ohio Chair of the College Democrats. Whaley is also a four-time delegate to the Democratic National Convention, worked for John Kerry's presidential campaign, and served as a presidential elector.

Ahead of the 2018 election cycle, Whaley considered a run for Congress before declaring her candidacy for Governor of Ohio. On May 8, 2017, Whaley announced that she was running for Governor in the 2018 election on a platform of job creation. She dropped out of the race on January 12, 2018, and endorsed Richard Cordray.