Patty Mills has helped the San Antonios Spurs to a 143-142 win with a game-winning two-pointer with seven seconds left in overtime.
Mills had the final score of the game to ensure a win for the Spurs and leave the Lakers winless.
The Aussie had 12 points, two rebounds and three assists in 31 minutes of game time.
It marks a 0-3 start for LeBron James and the Lakers, the first time James has started a season 0-3 since 2004/05.
He hit a three-pointer to take the game to overtime, but missed two free throws before Mills' shot and another three-point attempt right at the buzzer.
James had 32 points, eight rebounds and 14 assists, while Kyle Kuzma landed 37 points for the Lakers, as did LaMarcus Aldridge for the Spurs.