After Megamind, a highly intelligent alien supervillain, defeats his long-time nemesis Metro Man, Megamind creates a new hero to fight, but must act to save the city when his "creation" becomes an even worse villain than he was.
| Actor | Role |
|---|---|
 Will FerrellMegamind (voice) | Megamind (voice) |
 Brad PittMetro Man (voice) | Metro Man (voice) |
 Tina FeyRoxanne Ritchi (voice) | Roxanne Ritchi (voice) |
 Jonah HillTighten (voice) | Tighten (voice) |
 David CrossMinion (voice) | Minion (voice) |
 Ben StillerBernard (voice) | Bernard (voice) |
 Justin TherouxMegaminds's Father (voice) | Megaminds's Father (voice) |
 Jessica SchulteMegamind's Mother (voice) | Megamind's Mother (voice) |
 Tom McGrathLord Scott / Prison Guard (voice) | Lord Scott / Prison Guard (voice) |
 Emily NordwindLady Scott (voice) | Lady Scott (voice) |
 J.K. SimmonsWarden (voice) | Warden (voice) |
 Ella StillerSchoolchild (voice) | Schoolchild (voice) |
| QQuinn Dempsey StillerSchoolchild (voice) | Schoolchild (voice) |
 Brian HopkinsPrisoner (voice) | Prisoner (voice) |
 Christopher KnightsPrison Guard (voice) | Prison Guard (voice) |
 Mike MitchellFather in Crowd (voice) | Father in Crowd (voice) |
| JJasper Johannes AndrewsCrying Baby (voice) | Crying Baby (voice) |
 Jack BlessingNewscaster (voice) | Newscaster (voice) |
 Stephen KearinMayor (voice) | Mayor (voice) |