- Kumail Nanjiani - Samir Wassan
- Adam Scott - Justin Sanderson
- Sanaa Lathan - Nina Harrison
- Damson Idris - Dorian Harrison
- Tracy Morgan - J.C. Wheeler
- Amara Karan - Rena
- Diarra Kilpatrick - DiDi Scott
- Toby Hargrave - Joe Donner
- Chris Diamantopoulos - The 'Pilot'
- Katie Findlay - Air Hostess
- Nicholas Lea - Captain Donner
- China Shavers - Air Marshal
- J. Cameron Barnett - Flight Attendant Nick
- Greg Zach - Suspicious Punk
- Vladimir Ruzich - Tsezar
- Alexander Mandra - Igor Orlov
- Demelza Randall - Mandy
- Glenn Fleshler - Officer Lasky
- Steve Harris - Uncle Neil
- Candus Churchill - Mabel
- Henry Mah - Medical Examiner
- Steven Yeun - The Traveler
- Greg Kinnear - Captain Lane Pendleton
- Marika Sila - Sergeant Yuka Mongoyak
- Patrick Gallagher - Jack Mongoyak
- Jill Teed - Dotty Matheson
- Eric Keenleyside - Mayor Matheson
- Trevor Lerner - Trooper Samuels
- Taissa Farmiga - Annie
- Ike Barinholtz - Mike
- Luke Kirby - Dylan
- Rhea Seehorn - Martha
- John Cho - Raff Hanks
- Jacob Tremblay - Oliver Foley
- Allison Tolman - Maura McGill
- Kimberley Sustad - Helen Foley
- Lane Edwards - Joseph Foley
- Erica Tremblay - Lily Foley
- John Larroquette - President James Stevens
- DeWanda Wise - Alexa Brandt
- Jefferson White - Jerry
- Jonathan Whitesell - Casey Donlin
- Lucinda Dryzek - Katherine Langford
- Joyce Kurtz - Tina (voice)
- Percy Hynes White - Cole
- Peter Kelamis - Phil Smith
- Steph Song - Olivia
- Agape Mngomezulu - Steve
- Jeff Gladstone - Perry Sullivan
- James Ralph - Bartender
- Ginnifer Goodwin - Eve Martin
- James Frain - Mr. Allendale
- Toby Levins - William Martin
- Zabryna Guevara - Anna Fuentes
- Karin Konoval - Aidia
- Michael Eklund - Otto
- Robert Mann - Mosher
- Art Kitching - HSI Agent
- Iris Paluly - Female HSI Agent
- Shalyn Ferdinand - Monica Jones (uncredited)
- Shalyn Ferdinand - Young Intern
- Zazie Beetz - Sophie Gelson
- Seth Rogen - Adam Wegman / Himself
- Jason Priestley - Himself
- Caitlin Stryker - Anna
- Betty Gabriel - Herself
- Jimmi Simpson - Phil
- Gillian Jacobs - Annie
- Morena Baccarin - Michelle Weaber
- Colman Domingo - Carl Weaber
- Tony Hale - Tom
- Ethan Embry - Harry
- Jurnee Smollett - Jasmine
- Kylie Bunbury - Claudia
- Topher Grace - Mark
- Gretchen Mol - Mrs. Janet Warren
- Greta Lee - Mrs. Jones
- Abbie Hern - Madison
- Darren Dolynski - Reginald
- Osgood Perkins - Kanamit #2
- Paolo Maiolo - Officer Tyler
- Esther Ming Li - Lisa
- Anthony Harrison - Security Guard
- Christina Jastrzembska - Mrs. Turner
- Ingrid Libera - Earbud Model
- Serinda Swan - Ellen Lowell
- Hamza Fouad - Geoffrey
- Jaycie Dotin - Kelly Fox
- Natalie Goyarzu - Diane Desmond
- Kristin Lehman - Therapist
- Mike Dopud - Annie's Husband
- Emily C. Chang - Barista Lady
- Sara Amini - Julia
- Lossen Chambers - Mrs. King
- Jamall Johnson - Handsome Guy
- Simon Chin - Ice Cream Server
- Matthew Mandzij - Officer #1
- Nicole Major - Female Passenger
- Jessica Williams - Rei Tanaka
- Luisa d'Oliveira - Grace Niu
- Madeleine Kelders - Female Interviewee #6
- Alex Kim
Steve Harris interpreta a Uncle Neil en la serie.
Ginnifer Goodwin interpreta a Eve Martin en la serie.
Jordan Peele hace el papel de Self - Host.
Eric Keenleyside interpreta a Mayor Matheson en la serie.
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