The district takes in a portion of eastern and central Indiana as of the 2020 census, including Columbus and Richmond, some of Cincinnati's Indiana suburbs, most of Indianapolis's southern suburbs, and a sliver of Indianapolis itself.

The district is currently represented by Republican Jefferson Shreve, who was elected in 2024 after the retirement of Greg Pence, the brother of former U.S. Vice President Mike Pence, who represented this district before serving as Governor of Indiana and Vice President of the United States.

It includes Fayette, Hancock, Henry, Johnson, Rush, Shelby, Union, and Wayne counties, and parts of Bartholomew, Marion, and Randolph counties.

The 6th district takes in most of the city of Beech Grove as well as the south side of Indianapolis, encompassing Decatur, Perry, and Franklin Townships.

Several eastern and southern Indianapolis suburbs, including Greenwood, Franklin, and Greenfield, are also in the 6th district.