Indiana's 6th congressional district covers the western portion of the state, sandwiched between the cities of Indianapolis and Cincinnati. The only major city it contains is Muncie, but the suburbs of Indianapolis and Cincinnati make it so that 60% of the population lives in an urban area. This district was the most Republican district in Indiana in the 2016 presidential election: it voted for Trump by a margin of 40 points

Republican incumbent Luke Messer did not run for reelection in order to run of the Senate. The Republican nominee is Greg Pence, a businessman who is the brother of Vice-President and former Indiana governor Mike Pence. He will be running against Democrat Jeannine Lee Lake, a newspaper letter.