Assistant coach Claude Noel was chosen to lead the team on an interim basis.
General manager Scott Howson announced the firing a day after the struggling Blue Jackets blew a 1-0 lead in a listless 5-1 loss at Colorado. Columbus stands 14th of the 15 teams in the Western Conference with a 22-27-9 record and 53 points.
"It wasn't working," Howson said. "The team wasn't responding to the message."
The Blue Jackets play their next game at home against Dallas on Thursday night.
"You're going to see some changes," Noel said. "But I'm not going to reinvent the game."
The 54-year-old Noel joined the Blue Jackets as an assistant coach in June 2007, after spending four seasons as the head coach of the American Hockey League's Milwaukee Admirals. During that time, he led the club to a 183-94-12-31 regular-season record, three 100-point seasons and two West Division titles.
Built around star forward Rick Nash, the Blue Jackets made it to the first round of the Stanley Cup playoffs a year ago before being swept by the Detroit Red Wings.
"This is an emotional day for me," Noel said. "Ken Hitchcock is a friend of mine. He's a tremendous coach. I've been blessed to be able to learn from him. This is a sad day."
Hitchcock picked up his 500th career victory behind the Columbus bench a year ago, but the team appeared stagnant after a fast start this season.
The club got off to a 12-6-2 record through Nov. 19, but then wilted. The Jackets won just three of their next 24 games, spiraling out of the playoff picture. The defense sagged at times and even when last year's rookie of the year, goalie Steve Mason, had a good game, the offense fell apart.
"We don't consider the season lost," Howson said. "We'll play hard the rest of the season and see what happens."
Asked why he decided to fire Hitchcock now, Howson said, "We thought Hitch deserved a chance to work out these last 37 games. We kept hoping he'd find a decision."
The fourth coach in Blue Jackets history, Hitchcock had a record of 533-372-136 in 1,041 regular-season NHL games with the Dallas Stars, Philadelphia Flyers and Blue Jackets. He led the Stars to a Stanley Cup title in 1999.
With the Blue Jackets, he was 125-123-36. They had their finest season ever a year ago, when they went 41-31-10 (92 points).
Hitchcock's contract runs through the 2011-12 season at $1.3 million per season.
He did not immediately return a call seeking comment.
"Ken Hitchcock joined the Blue Jackets at a time when our team needed credibility, stability and structure, which is exactly what he provided and for that we are extremely grateful," Blue Jackets president Mike Priest said.