Perrino's acting career began with his portrayal of Lorenzo "Shakes" Carcaterra, one of the lead roles in the film Sleepers.
Perrino went on to work with Anna Paquin, playing her love interest, Ross Epstein, in Tony Goldwyn's A Walk on the Moon.
Perrino moved on to the indie film The Bumblebee Flies Anyway, playing Mazzo, a terminally ill cancer patient dealing with his last days on earth.
After a hiatus from acting, Perrino returned to appear in the last season of The Sopranos, playing Jason Gervasi, a young mobster.
In 2017, Perrino began work on the STARZ network's hit crime series Power in its 5th season as Vincent Ragni, a boss in the Italian syndicate.