The shock announcement came after a 6-1 home win over Sporting Gijon at Camp Nou, which saw Barca regain the La Liga lead by two points from Real Madrid, albeit having played two games more. Lionel Messi, Luis Suarez and Neymar were all on target in the victory.
Enrique, pictured, has won eight trophies since taking charge, including the Champions League.
He initially signed a two-year deal before agreeing a one-year extension at the end of a first season in which he won the treble.
Barca president Josep Maria Bartomeu had spoken of his wish to keep the 46-year-old, but now he must look for a new boss.
The news will immediately ignite speculation over who will succeed Enrique at the Nou Camp. Sevilla’s former Chile boss Jorge Sampaoli is among the early favourites.
Everton’s former Barcelona defender Ronald Koeman is another who has been linked with the job. Tottenham manager Mauricio Pochettino, who made his name across the city from Barca at Espanyol, has previously been mentioned as a possible candidate.
There is likely to be no shortage of other candidates, with Arsene Wenger among them.
Arsenal boss Wenger is out of contract at the end of the season and says he will still be in management even if he leaves the Gunners when his contract expires at the end of this season after 20 years in charge.
Bartomeu said on Barcelona’s official Twitter feed: “We accept Luis Enrique’s decision. He has been a great coach. Now it is time to end his spell in the best possible way.
“Luis Enrique has brought us great success and he can still bring us more. The players are motivated to do it.”