- Joaquin Phoenix as Theodore Twombly[8]
- Scarlett Johansson as Samantha (voice)[8]
- Amy Adams as Amy[8]
- Rooney Mara as Catherine Klausen[8]
- Olivia Wilde as Blind Date[9]
- Matt Letscher as Charles[10]
- Luka Jones as Mark Lewman[11]
- Chris Pratt as Paul[12]
- Kristen Wiig as Sexy Kitten (voice)[13]
- Bill Hader as Chat Room Friend #2 (voice)[13]
- Portia Doubleday as Isabella[14]
- Soko as Isabella (voice)
- Brian Cox as Alan Watts (voice)[14]
- Spike Jonze as Alien Child (voice)[15]
- Steve Zissis as New Sweet Boyfriend of Mother Who Dated Pricks
- Alia Janine as Commuter (uncredited)
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