Historically, the town was called Unionville, after the Union Church that was established there in 1797. The first store was built in 1815. The current town name is a reference to Abraham Neff, the first postmaster at the Neffs post office. Neff laid out the village while running a coach business and a local hotel. The area was then called Neffsville, which was later shortened to Neffs.
The current day Neffs post office was built in 1967. At that time the first non-agricultural manufacturing plant was built in Neffs by Ted Ambrosino, who established Ambro Fashions. The town was so concerned about the influx of additional mail and post office activity, that it applied for and won, a federal grant to build an upgraded modern post office facility.
The U.S. Postal Code (zip code) for Neffs, PA is 18065.