The decision comes in the wake of Saturday's 1-0 defeat away to Coventry City, a result which left Boro in the Championship relegation zone with only 10 points from their opening 11 fixtures.
The Teesside club narrowly missed out on the playoffs with a seventh-placed finish under Wilder last season, but have endured a poor start to the new campaign with only two wins to their name so far.
Boro have not lost back-to-back league games yet this season, but a run of just four wins and 18 points from their last 19 league games stretching back to last season ultimately spelled the end for Wilder.
Leo Percovich will take over the first team as interim boss while the search for a new manager gets underway, with Craig Liddle, Mark Tinkler and Lee Cattermole assisting the temporary manager.
"Middlesbrough Football Club have terminated the contract of manager Chris Wilder with immediate effect," read a statement on the club's official website.
"Leo Percovich will take over first team affairs in the interim basis, assisted by Craig Liddle, Mark Tinkler and Lee Cattermole.
"The club would like to place on record its thanks to Chris and his staff for all their hard work over the past 11 months."
Wilder took over at the Riverside last November and leaves having won 18, drawn 11 and lost 16 of his 45 matches at the helm - a win percentage of 40%.
Rob Edwards, who was sacked by Watford just last week, is thought to be the front-runner to replace Wilder and could be interviewed as early as this week.
Gary O'Neil, who is currently in temporary charge of Bournemouth and was nominated for the September Premier League Manager of the Month award, has also been mentioned as a possible candidate for the job.