"Don't Play No Game That I Can't Win" received generally positive reviews from critics, who praised Santigold's guest appearance and its reggae feel. Dave Simpson of The Guardian wrote: "Santigold gives 'Don't Play No Game That I Can't Win' some instantly infectious pop reggae sunshine." Kyle Anderson of Entertainment Weekly praised the song, calling it "a perfect reggae-kissed summer jam". Matt Diehl of the Los Angeles Times called Santigold's guest appearance memorable, and wrote that she added to the track "Brooklyn dancehall fire and a welcome feminine contrast to the b-boy stances." Mark Richardson of Pitchfork Media wrote that the pairing between the Beastie Boys and Santigold on the track "feels natural and obvious", adding that one "could argue that the Beastie Boys' polyglot approach in the 90s helped clear the way for her style, which mixes an ear for the sound of other cultures with a touch of Lower East Side artiness."
The music video for "Don't Play No Game That I Can't Win" was directed by the group's longtime collaborator Spike Jonze. In the video, the Beastie Boys, along with Santigold, are portrayed in action figure form.