 Diego LunaManolo (voice) | Manolo (voice) |
 Channing TatumJoaquin (voice) | Joaquin (voice) |
 Zoe SaldañaMaria (voice) | Maria (voice) |
 Christina ApplegateMary Beth (voice) | Mary Beth (voice) |
 Eugenio DerbezChato (voice) | Chato (voice) |
 Cheech MarinPancho Rodriguez (voice) | Pancho Rodriguez (voice) |
 Gabriel IglesiasPepe Rodriguez (voice) | Pepe Rodriguez (voice) |
 Ron PerlmanXibalba (voice) | Xibalba (voice) |
 Kate del CastilloLa Muerte (voice) | La Muerte (voice) |
 Ana de la RegueraCarmen Sánchez (voice) | Carmen Sánchez (voice) |
 Dan NavarroChakal (voice) | Chakal (voice) |
 Ice CubeCandle Maker (voice) | Candle Maker (voice) |
 Héctor ElizondoCarlos Sanchez (voice) | Carlos Sanchez (voice) |
 Danny TrejoSkeleton Luis (voice) | Skeleton Luis (voice) |
 Carlos AlazraquiGeneral Posada / Dali / Chuy (voice) | General Posada / Dali / Chuy (voice) |
| EEmil-Bastien BouffardYoung Manolo (voice) | Young Manolo (voice) |
 Elijah RodriguezYoung Joaquin | Young Joaquin |
| GGenesis OchoaYoung Maria (voice) | Young Maria (voice) |
 Plácido DomingoSkeleton Jorge (voice) | Skeleton Jorge (voice) |
 Grey DeLisleGrandmother (voice) (as Grey Griffin) | Grandmother (voice) (as Grey Griffin) |
| TTrey BumpassGoth Kid / Orphan | Goth Kid / Orphan |
 Miguel SandovalLand of the Remembered Captain (voice) | Land of the Remembered Captain (voice) |
 Ben GleibGoya / Dali (voice) | Goya / Dali (voice) |
| RRicardo El Mandril SanchezPablo Rodriguez (voice) | Pablo Rodriguez (voice) |
| IIshan SharmaSanjay | Sanjay |
 Jorge R. GutierrezSkeleton Carmelo (voice) | Skeleton Carmelo (voice) |
 Anjelah Johnson-ReyesAdelita / Nina (voice) | Adelita / Nina (voice) |
| KKennedy PeilSasha (voice) | Sasha (voice) |
 Sandra EquihuaScardelita (voice) | Scardelita (voice) |
| CCallahan ClarkJane (voice) | Jane (voice) |
