In antiquity, much of the Tiber trade took place here, and the remains of broken clay vessels (amphorae) were stacked creating the artificial Testaccio hill, which today is a source of much archaeological evidence as to the history of ancient everyday Roman life.

Until the urban recovery that took place after 1870, which destined a huge area to industrial and manufacturing purposes, the borough was chiefly inhabited by poor farmers and shepherds, it was vulnerable to the Tiber floods and infested by malaria.

The portion of the rione, inside the Aurelian Walls, is born as a residential extension of the productive area, housing the laborers of the several industries that arose at the end of 19th century by the side of Via Ostiense.

Albeit until 1921 the rione was administratively a portion of Ripa, Testaccio has always had a strong identity, even if it had often a bad reputation, especially due to the countless traffics that took place in the harbor.

In 1884 an inquiry launched by the municipality bestowed on Testaccio the national record in alcohol usage, while between the 1980s and the 90s it was the stronghold of the so-called Testaccini, a branch of the Banda della Magliana.