Khambatta made her Hollywood début in director K. A. Abbas's Bambai Raat Ki Bahon Mein (1968), playing cabaret singer Lily who croons the film's title track. She had small roles in Conduct Unbecoming and The Wilby Conspiracy (both 1975). She went on to have a brief movie career that included the role for which she is most recognized, the bald Deltan navigator Lieutenant Ilia, in Star Trek: The Motion Picture (1979). She shaved her head for the role. She was originally signed to play the role for five years, as the intention was to create a new Star Trek television series. Khambatta said that she was thrilled when the project became a movie instead, because it would have greater impact on her career, but she also recognised that she had lost five years' work. Khambatta became the first Indian citizen to present an Academy Award in 1980. She was nominated for Saturn Award for Best Actress for her role in Star Trek. This led to roles in Nighthawks (1981), Megaforce (1982), Warrior of the Lost World (1983), and She-Wolves of the Wasteland (1988). She was considered for the title role in the James Bond film Octopussy (1983), but was passed over in favor of Maud Adams.