- Tom Holland Peter Parker / Spider-Man
- Samuel L. Jackson Nick Furia
- Zendaya Michelle Jones
- Cobie Smulders Maria Hill
- Jon Favreau Happy Hogan
- J.B. Smoove Mr. Dell
- Numan Acar Dimitri
- Marisa Tomei May Parker
- Jake Gyllenhaal Quentin Beck / Mysterio
- Angourie Rice Betty Brant
- Martin Starr Mr. Harrington
- Tony Revolori Flash Thompson
- Jacob Batalon Ned Leeds
- Jorge Lendeborg Jr. Jason Ionello
- J.K. Simmons J. Jonah Jameson
- Clare Dunne Victoria
- Anjana Vasan
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