- Daniel Craig as Benoit Blanc, a private detective
- Chris Evans as Hugh Ransom Drysdale, Linda and Richard's son
- Ana de Armas as Marta Cabrera, Harlan's nurse
- Jamie Lee Curtis as Linda Drysdale, Harlan's eldest daughter
- Michael Shannon as Walt Thrombey, Harlan's youngest son
- Don Johnson as Richard Drysdale, Linda's husband
- Toni Collette as Joni Thrombey, the widow of Harlan's deceased son Neil
- LaKeith Stanfield as Detective Lieutenant Elliott
- Katherine Langford as Meg Thrombey, Joni's daughter
- Jaeden Martell as Jacob Thrombey, Walt's son
- Frank Oz as Alan Stevens, Harlan's counsel
- Riki Lindhome as Donna Thrombey, Walt's wife
- Edi Patterson as Fran, Harlan's housekeeper
- K Callan as Wanetta "Great Nana" Thrombey, Harlan's mother
- Noah Segan as Trooper Wagner, a police officer
- Christopher Plummer as Harlan Thrombey, an 85-year-old best-selling crime novelist.
- M. Emmet Walsh as Mr. Proofroc, a security guard
- Marlene Forte as Mrs. Cabrera, Marta's mother
- Shyrley Rodriguez as Alice Cabrera, Marta's sister
- Kerry Frances as Sally, Alan's assistant
- Joseph Gordon-Levitt as Detective Hardrock (voice cameo)
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