The 60-year-old took charge of his 1,000th game as a manager in Sunday's 3-2 defeat to Tottenham Hotspur, which also marked the first Magpies clash under the new Saudi-backed ownership.
However, Bruce was widely expected to depart following the arrival of the club's new owners, and Newcastle announced on Wednesday morning that the three-time Premier League winner had left his post.
"I am grateful to everyone connected with Newcastle United for the opportunity to manage this unique football club," Bruce said in a statement on the official Newcastle United website.
"I would like to thank my coaching team, the players and the support staff in particular for all their hard work. There have been highs and lows, but they have given everything even in difficult moments and should be proud of their efforts.
"This is a club with incredible support, and I hope the new owners can take it forward to where we all want it to be. I wish everyone the very best of luck for the rest of this season and beyond."