Perlman is a frequent collaborator of Hellboy director Guillermo del Toro, having roles in his films Cronos (1993), Blade II (2002) and Pacific Rim (2013). He is also known for his voice-over work as the narrator of the post-apocalyptic game series Fallout, Clayface in Batman: The Animated Series, Slade in the animated series Teen Titans, and The Stabbington Brothers in Disney’s animated film Tangled (2010).
His breakthrough role came when he played Vincent in the TV series Beauty and the Beast, opposite Linda Hamilton from 1987 to 1990. This earned him a Golden Globe for Best Performance by an Actor in a Television Series in 1989. Other television credits include Highlander: The Series as The Messenger, The Outer Limitsas Lt. Col. Brandon Grace on the episode “Black Box” and a starring role as Josiah Sanchez in The Magnificent Seven, alongside Michael Biehn and Laurie Holden. His most notable film appearances were in films such as The Adventures of Huck Finn (1993), The Island of Dr. Moreau (1996), Alien Resurrection (1997), Enemy at the Gates (2001), and Star Trek Nemesis (2002). In 2015, he played in Stonewall, a drama film directed by Roland Emmerich and filmed in Montreal, which also stars Jeremy Irvine, and Jonathan Rhys Meyers.
His most recent work include the film Fantastic Beasts and Where to Find Them (2016). He also voiced Bular in Trollhunters, John Goodspeed in Final Space, and Optimus Primal in Transformers: Power of the Primes.