The 41-year-old has been told that he is no longer employed by the club, with the decision coming on Monday.
His team could only manage a scoreless draw against Millwall on Saturday in the Championship, which puts them in 23rd position.
The club want to ensure there is no relegation dogfight all season, which looked the case with Monk in charge.
Monk had been with the club since arriving in September 2019.
He managed 58 games, with only 18 wins coming during that spell.
Chairman Dejphon Chansiri told swfc.co.uk: "I feel the time is right to make a change and I wish Garry and his team all the best for the future.
"I would like to say thank you for the time and effort Garry and his staff have committed to Sheffield Wednesday."