The name Nerola is probably derived from the Sabine word nero or nerio, which meant "strong" and "brave".

Traces of a Roman era villa have been found on that site, which legend attributes as belonging to Nero himself.

This may have been the seat of the bishopric called Aquaviva in Latin, whose bishops took part in synods held in Rome in the second half of the 5th century and the beginning of the 6th: Paulus or Paulinus in 465, Benignus in 487, 497, and 502, and Bonifacius in 503.

At the end of the 15th century, the castle was subsequently reinforced with strong towers and other defensive fortifications around the village.

During the COVID-19 pandemic, Nerola suffered a particularly high infection rate, and was entirely quarantined by authorities around the end of March 2020.