Schmidt is the second female Ohio Republican to be elected to Congress without succeeding her husband and the first woman to represent the Cincinnati area in the House. She won the Ohio 2nd congressional district seat in a special election on August 2, 2005, by 3.5 percentage points over Democrat and Iraq War veteran Paul Hackett, amid national attention to the race because of Hackett's strong views on the war. The margin of her victory led many Democrats to claim a victory for their party, since the district had been reliably Republican for the past 30 years, and to forecast trouble for the Republicans in 2006. Despite these forecasts, Schmidt defeated former representative Bob McEwen in a Republican primary in May 2006 and Democrat Victoria Wells Wulsin, a medical doctor, in 2006 with 50.4% of the vote. She was re-elected in 2008, winning with 45% of the vote, and in 2010, winning with 58.6%. On March 6, 2012, Schmidt was defeated for re-election in the GOP primary by Brad Wenstrup. In 2020 she ran for and won the 65th district Ohio House seat with 65% of the vote, after being backed by the embattled Speaker Larry Householder.