- Rainn Wilson - Harry Mudd
- Doug Jones - Saru
- Mary Wiseman - Sylvia Tilly
- Yadira Guevara-Prip - Me Hani Ika Hali Ka Po
- Mimi Kuzyk - Siobhan Tilly
- Aldis Hodge - Craft
- Annabelle Wallis - Zora (voice)
- Samora Smallwood - Lt. Amin
- Rosa Salazar - Lynne Lucero
- H. Jon Benjamin - Edward Larkin
- Lisa Michelle Cornelius - Sarah
- Hannah Spear - Siranna
- Michelle Yeoh - Philippa Georgiou
- Ethan Peck - Spock
- Rebecca Romijn - Number One
- Amrit Kaur - Cadet Thira Sidhu
- Steve Boyle - Security Officer #1
- Colette Whitaker - Station 28 Computer (voice)
- Robert Verlaque - Aradar
- Robert Verlaque - Principal
- Kenric Green - Mike Burnham (voice)
- Kyrie McAlpin - Young Michael Burnham (voice)
- Joy Castro - Mom
- Andrea Davis - Teacher
- Jason Deline - Dad
- Ilamaria Ebrahim - Kima
- Sadie Munroe - Lil
- Milton Barnes - Dock Crew #1
- Joe Delfin - Worker Bee #1
- Julianne Grossman - Discovery Computer (voice)
- Kirk R. Thatcher - Narrator (voice)
- Jenette Goldstein - USS Enterprise Computer (voice)
- Ricardo Montalban - Khan (voice) (archive footage)
- William Shatner - Capt. James T. Kirk (voice) (archive footage)
- George Takei - Hikaru Sulu (voice) (archive footage)
- Gioya Tuma-Waku - Multiple (voice)
- Anson Mount - Christopher Pike
Ricardo Montalban hace el papel de Khan (voice) (archive footage).
Michelle Yeoh interpreta a Philippa Georgiou en la serie.
Jenette Goldstein interpreta a USS Enterprise Computer (voice) en la serie.
William Shatner interpreta a Capt. James T. Kirk (voice) (archive footage) en la serie.
George Takei interpreta a Hikaru Sulu (voice) (archive footage) en la serie.
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