After Haas driver Kevin Magnussen changed lanes in the opening sprint, Alexander Albon, in a Williams, moved and collided with the other Haas, driven by Nico Hulkenberg.
The out of control cars then took out Magnussen.
While Hulkenberg remained on track, Albon and Magnussen went off heavily, damaging their cars and spraying debris and tyres.
The race was red-flagged to clean up the mess on the Interlagos track in Sao Paulo.
Daniel Ricciardo's Alpha Tauri was hit by a flying tyre and had to return to the pits for repairs.
The race restarted at 14:34 local time (17:34 GMT) with Magnussen and Albon out of the race.
Charles Leclerc was not in the field after he lost control of his Ferrari on the formation-up lap before the initial start, which meant he was not allowed to rejoin even if his car could have been repaired.