Kevin Lowe, Oilers president of hockey operations, said he informed Tambellini of his decision Sunday.
"Steve's a very good man, worked hard for the Oilers and I want to thank him for his contributions to the hockey team for the last five years," Lowe said.
Tambellini, 54, was named general manager of the Oilers on July 31, 2008, replacing Lowe in the position. Edmonton has qualified for the NHL playoffs since 2006 and is 16-18-7, which is 12th in the NHL's Western Conference with seven games to play.
The top eight teams in each conference advance to the playoffs.
"Despite showing improvement in areas this season, we are not where we want to be right now, nor where we should be," Lowe said. "We feel strongly we need to make changes right now."
MacTavish, also 54, played for five NHL teams over a 19-season career. None of those seasons was with Edmonton. He was the Oilers' coach 2000-09, winning 301 games and advancing the Stanley Cup finals in 2006.