- Megan Fox April O'Neil
- Will Arnett Vern Fenwick
- William Fichtner Eric Sacks
- Alan Ritchson Rafael
- Noel Fisher Michelangelo
- Pete Ploszek Leonardo
- Jeremy Howard Donatello
- Abby Elliott Taylor
- Whoopi Goldberg Bernadette Thompson
- Danny Woodburn Splinter
- Minae Noji Karai
- Johnny Knoxville Leonardo (voz)
- Tony Shalhoub Splinter (voz)
- Venida Evans Subway Hostage