On-loan defender Baba Rahman scored the only goal as Schalke got their Europa League Group I campaign off to a winning start in Nice.
The 21-year-old scored his first goal for the club in just his third appearance, having failed to do so in 23 games for his parent club Chelsea last season.
For once Mario Balotelli, whose two goals on his debut for the Ligue 1 club inspired them to victory at the weekend, did not grab the headlines.
The Italy international, who played the full 90 minutes, was quiet in the first half and managed only two shots after the break.
Rahman struck with 15 minutes remaining, firing home from the left side of the penalty area after being set up by Germany international Max Meyer.
Eric Maxim Choupo-Moting almost doubled the visitors' lead in added time but saw his shot rebound off a post.