Holmesburg is often associated with William Penn’s surveyor, Thomas Holme, but the neighborhood is named after the Holme family, which bought many estates along Frankford Avenue and Pennypack Creek. Several famous people, including Matthias Baldwin, Stephen Decatur, and Ethel Barrymore, are from this area. Holmesburg is also known for being among the oldest, most continually occupied African-American communities in the United States.

Today, Holmesburg is considered the area between Roosevelt Boulevard to the west, Sheffield to the south, and the Delaware River to the east, and is bordered by Torresdale to the north.