The 29-year-old was replaced by Ishak Belfodil in the 19th minute after landing awkwardly following a challenge with Schalke defender Thilo Kehrer.
He was subsequently taken to hospital, where the diagnosis was confirmed. He will undergo surgery in Bremen later on Saturday before beginning a two-month recovery process.
"His injury is a big loss," said Head coach Alexander Nouri after the game. "Everyone knows his value to the side. We hope that he'll be fit again soon."
Despite going 1-0 up shortly after Kruse's substitution, Bremen slipped to a 2-1 defeat and are now second bottom of the Bundesliga table with just one point from four games.
Watch: Kruse and Co. reveal how they'd rate themselves in FIFA 18