Natalie Cook (Cameron Diaz), Dylan Sanders (Drew Barrymore) and Alex Munday (Lucy Liu) are the "Angels", three intelligent, talented, tough, attractive women who work as private investigators together for an unseen millionaire named Charlie (voiced by John Forsythe). Charlie uses a speaker in his offices to communicate with the Angels, and his assistant Bosley (Bill Murray) works with them directly when needed.
Charlie assigns the Angels to find Eric Knox (Sam Rockwell), a software genius who created a revolutionary voice-recognition system and heads his own company, Knox Enterprises. Knox is believed to have been kidnapped by Roger Corwin (Tim Curry), who runs a communications-satellite company called Redstar. The Angels infiltrate a party held by Corwin and spot the Creepy Thin Man (Crispin Glover) who was seen on the surveillance videos during Knox's kidnapping. They chase and fight the Creepy Thin Man, but he runs away. When they follow him, they discover Knox.