Cobbs Creek was known as Karakung by the Lenni Lenape Indians and Mill Creek by Swedes in the late 1600's. It later became known as Cobbs Creek after an English settler. The neighborhood surrounding the Cobbs Creek Branch was part of land belonging to the Hoffman family since colonial days. The area became part of Blockley Township in the 1800's.

A village called Angora centered around several mills on Cobbs Creek located at the current intersection of 60th Street and Baltimore Avenue. The woods surrounding the village were known as Sherwood Forest. In the 1910's, the mills and woods were torn down to make way for houses.

Baltimore Avenue was used to transport food and supplies from the Schuylkill River wharfs to places west of the city. Around 1905, the Philadelphia Rapid Transit Company started subway surface routes using the electric streetcar on Baltimore Avenue. Trolleys still travel this route today. Subway surface routes, as well as the completion of the Market Elevated in 1907, spurred residential construction in the Cobbs Creek neighborhood.

Funded by a grant from Andrew Carnegie, the Cobbs Creek Branch opened on December 30, 1925. The community contributed $10,000 toward a book fund. The building was renovated and refurbished in 1957.

In 1990, the branch library was renamed the Blanche A. Nixon/Cobbs Creek Branch in honor of Blanche Nixon, a local resident, community activist and library volunteer. Mrs. Nixon spearheaded beautification projects at the branch, including its garden and exterior mural.

The library was renovated in 1997 as part of the "Changing Lives" campaign, which refurbished branches and brought Internet service to every library.