- Ben Affleck as Nicholas "Nick" Dunne, a professor[7]
- Rosamund Pike as Amy Elliott Dunne, Nick's missing wife
- Neil Patrick Harris as Desi Collings, Amy's wealthy ex-boyfriend
- Tyler Perry as Tanner Bolt, Nick's attorney
- Carrie Coon as Margo "Go" Dunne, Nick's twin sister[7]
- Kim Dickens as Detective Rhonda Boney, the lead investigator on Amy's disappearance
- Patrick Fugit as Officer James Gilpin, Boney's partner
- Missi Pyle as Ellen Abbott, a cable TV host based on Nancy Grace[8]
- Emily Ratajkowski as Andrea "Andie" Fitzgerald, Nick's mistress and student
- Casey Wilson as Noëlle Hawthorne, Nick and Amy's pregnant neighbor
- Lola Kirke as Greta, a young woman Amy meets at the Ozarks campground
- Boyd Holbrook as Jeffrey "Jeff", a flirtatious man Amy meets at the Ozarks campground
- Lisa Banes as Mary Elizabeth "Marybeth" Elliott, Amy's mother
- Sela Ward as Sharon Schieber, a network TV host
- Scoot McNairy as Thomas "Tommy" O'Hara, another former boyfriend of Amy's
- Scott Takeda as TV Producer
- David Clennon as Randall "Rand" Elliott, Amy's father
- Kathleen Rose Perkins as Shawna Kelly
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