The NHL team made the announcement Monday on its Twitter account.
MacLean, 56, was in his fourth season as Ottawa's head coach.
He won the Jack Adams Award as the NHL's top coach in 2013, his second season with the Senators, and took an injury-ravaged team to the second round of the playoffs that year. The team rewarded him with a three-year contract extension that runs through 2016-17.
But Ottawa missed the playoffs last season and is currently outside of a playoff position with a record of 11-11-5, despite Sunday night's comeback overtime win over Vancouver.
MacLean finishes his Senators tenure with a regular-season record of 114-90-35.
A replacement was not immediately named, but assistant Dave Cameron is considered the leading candidate to take over on an interim basis.