Odette Annable ... Amata Almodovar (voice) (as Odette Yustman)

Jeff Baker ... Stanley Armstrong / Hannibal Hamlin / Sergeant RL-3 / Herman Gomez / Gary Staley / Button Gwinnett / Edgar Wellington II / Gary Clones / Mel / Ernest 'Uncle' Roe / Bannon / Dusty / Willy Wilson / Bronson / Stevie Mack / Paul Hannon Sr. / John Kendall / Officer Richards / Officer O'Brian / Officer Park / Officer Wolfe / Doc Hoff / Drifter / Knight Dillon / Henry Young / Ian West / Jack Smith / Jotun / Junders Plunkett / Knight Captain Colvin / Silas / Harkness (pre-transformation) / Branchtender Linden / Pappy / Frank / Paulie Cantelli / Roger Rockwell / Ronald Lauren / Rory McLaren / Scribe Bowditch / Stockholm / Micky / Carlos / Willy / Ymir / Scavengers / Brotherhood of Steel Initiates / Brotherhood of Steel Scribes / The Wasteland Junkie / Hunters / Hitmens / Escaped Slaves / Megaton Refugees / Wastelanders / Brotherhood Outcasts / Megaton Settlers / Patients / Tenpenny Tower Residents / Desmond Lockheart - Point Lookout DLC (voice)

William Bassett ... Elder Owyn Lyons (voice)

Karen Carbone ... Catherine - Mother / Moira Brown / Red / Suzie Mack / Sydney / Anna Holt / Belle Bonny / Brianna / Cherry / Crimson / Fantasia / Lana Danvers / Nova / Rosie / Susan Lancaster / Scribe Yearling / Rivet City Security Guards / Brotherhood of Steel Paladins / Brotherhood of Steel Knights / Brotherhood of Steel Initiates / Wastelanders / Caravan Guards / Children of the Atom / Escaped Slaves (voice)

Johnny Contino ... Grouse / Sam Warrick / Mad Johnny Wes / Regulators / Slavers / Wastelanders / Tenpenny Security Guards / Brotherhood Outcasts / Brotherhood of Steel Paladins / Brotherhood of Steel Knights / Brotherhood of Steel Initiates / Caravan Guards (voice)

Erik Dellums ... Three Dog (voice) (as Erik Todd Dellums)

Paul Eiding ... Nathan Vargas / Abraham Washington / Tree Father Birch / Evan King / Arkansas / Daniel Littlehorn / Dr. Zimmer / Walter / Father Clifford / Mister Lopez / Dr. Julius Banfield / Herbert Dashwood / Irving Cheng / Harris Smith / Breadbox / Tinker Joe / Officer Taylor / The Preacher / Bill Steward (voice)

Shari Elliker ... Beatrice Armstrong / Reilly / Star Paladin Cross / Victoria Watts / Bleak / Brailee Ewers / Brick / Carolina Red / Christie Young / Cindy Cantelli / Cutter / Knight Captain Dusk / Ellen DeLoria / Holly / Scribe Jameson / Janet Rockwell / Janice Kaplinski / Jenny Stahl / Jessica / Karen Schenzy / Kimba / Linda Smith / Lydia Montenegro / Mabel Henderson / Branchtender Maple / Martha Simpson / Martha Wilson / Mei Wong / Millicient Wellington / Defender Morgan / Pat Neusbaum / Silver / Simone Cameron / Sonora Cruz / Tammy Hargrave / Tanya 'The AntAgonizer' Christoff / Child Slaver / Wastelanders / Tenpenny Residents / Slavers / Brotherhood of Steel Paladins / Brotherhood of Steel Knights / Brotherhood of Steel Initiates / Brotherhood Outcasts / Captives / Female Raiders / Caravan Traders / Megaton Settlers / Hunter (voice)

Peter Gil ... Colonel Augustus Autumn / Confessor Cromwell (voice)

Gregory Gorton ... Jonas Palmer / Dave / Horace Pinkerton / Vance / Daniel Agincourt / Officer Armstrong / Protector Casdin / Doc Church / Crow / Branchtender Cypress / Dominic D'Ellsadro / Ken Ewers / Herman Gomez (Trouble on the Homefront) / Michael Hawthorne / Seagrave Holmes / Paladin Hoss / Anthony Ling / Lug-Nut / George Neusbaum / Scribe Peabody / Initiate Pek / Dr. Preston / Shorty / Leo Stahl / Leroy Walker / Sister / Carter / Laszlo Radford / John Malleus / Museum of Technology voiceover / Hunters / Caravan Traders / Megaton Settlers / Scavengers / Caravan Guards / Brotherhood of Steel Initiates / Brotherhood of Steel Scribes (voice)

Duncan Hood ... Overseer Alphonse Almodovar / Dukov / Scribe Reginald Rothchild / Tobar - Point Loockout DLC (voice)

Jake Howard ... One Year Baby (voice)

Jan Johns ... Lucy West / Clover / Sierra Petrovita / Alejandra Torres / Angela Staley / Bittercup / Christine Kendall / Knight Captain Durga / Machete / Mary Holden / Pepper Gomez / Shawna / Susie Mack / Trinnie / Vera Weatherly / Initiate Reddin / Specialist Olin - Operation Anchorage DLC (voice)

Luke Lafferty ... Young Paul Hannon Jr. (voice)

Jennifer Massey ... Doctor Madison Li (voice)

Pete Papageorge ... Chief Gustavo / Paladin Vargas / Allen Mack / Paladin Bael / Bill Foster / Brock / Caleb Smith / Defender Rococo Rockfowl / Forty / Garza / Knight Finley / Joe Porter / Irving Gallows / Lucky Harith / Scott 'The Mechanist' Wollinski / Paladin Kodiak / Donovan / Karl / Shrapnel / Ben Canning / Wastelander Captive / Wastelander (voice)

Stephen Russell ... Andy / Mister Buckingham / Harold / Wadsworth / Cerberus / Jones / Godfrey / Sawbones / Deputy Steel / Mr. Gutsy Robots / Mr. Handy Robots (voice)

Diana Sowle ... Old Lady Palmer / Agatha / Margaret Primrose / Manya Vargas / Old Lady Dithers / Leaf Mother Laurel / Mother Maya / Bloomseer Poplar / Tiffany Cheng / Child of Atom (voice)

Jakob Stalnaker ... Young Butch / Mayor Maccready / Jason Grant (voice)

Gus Travers ... Armitage / Butcher / Paladin Gunny / Flak / Paladin Glade / Knight Sergeant Wilks / Craterside Supplies Mercenary / Tenpenny Security Guards / Rivet City Security Guards / Slavers / Brotherhood Outcasts / Brotherhood of Steel Paladins / Brotherhood of Steel Knights / Brotherhood of Steel Initiates (voice)

Audrey Wasilewski ... Tulip / Greta / Carol / Willow / Nurse Graves / Miss Jeanette / Ethyl / Bessie Lynn / Female Ghouls (voice)

Bari Biern ... Catherine - Point Lookout DLC / Marguerite - Point Lookout DLC / S. Marcella J. - Point Lookout DLC / Nadine - Point Lookout DLC / Madame Panada - Point Lookout DLC / Woodrose - Point Lookout DLC / Chinese Instructor - Point Lookout DLC / Female Smuggler - Point Lookout DLC / Caroline Saunders- Point Lookout DLC / Female Tribal - Point Lookout DLC (voice)

Rest of cast listed alphabetically: