Ron Perlman has established a significant career as a voice actor in animation, including several prominent roles in anime and anime-influenced productions. Known for his deep, resonant voice, he has brought a variety of characters to life, often portraying imposing villains and authoritative figures.

Perlman has taken on a number of key roles in series that appeal to anime audiences. He is known to fans of the Transformers franchise for voicing Optimus Primal, the leader of the Maximals. He first voiced the character in the 2018 animated series Transformers: Power of the Primes and later reprised the role for the 2023 theatrical film Transformers: Rise of the Beasts. In the 2007 anime series Afro Samurai, which blends samurai action with hip-hop culture, he voiced Justice, the six-shooter-wielding gunman who serves as the primary antagonist and the target of the title character's quest for revenge. Additionally, he played Detective Netah in the 1995 film Crying Freeman, a live-action adaptation of the popular manga series.

Beyond these specific requests, Perlman's voice acting portfolio includes several other notable roles in anime and Western animation heavily inspired by Japanese aesthetics. He voiced The Lich, a powerful and ancient evil, in Adventure Time, a series known for its unique art style and storytelling. In the Teen Titans animated series, he provided the voice for Slade, a master strategist and one of the team's most formidable enemies. He also lent his voice to Fire Lord Sozin in the critically acclaimed series Avatar: The Last Airbender. His work in the DC Animated Universe, particularly as the tragic villain Clayface in Batman: The Animated Series, is also well-regarded by animation fans.

Throughout his career, Perlman has received recognition for his live-action performances, including a Golden Globe Award for his role in the television series Beauty and the Beast. His voice work, however, has become a significant part of his legacy, praised for adding depth and gravitas to characters ranging from monstrous villains to powerful heroes. His ability to convey both menace and world-weariness has made him a frequent and memorable presence in genre animation.