The Demons have been without a CEO since Cameron Schwab stepped down on April 9.
Jackson will take on the role from 1 May for six months, overseeing day to day operations through to the end of the season, and will also assist the Demons in the selection process for a full time CEO.
AFL CEO Andrew Demetriou endorsed Jackson's appointment in Sydney on Thursday.
"He's been one of the great CEO's of our competition when he was with the Essendon Football Club," he said.
"He's done some work for us recently, particularly through AFL Victoria and community football.
"He's very experienced, very strong and I think it's a great decision by the Melbourne Football Club."
After working in the mining and manufacturing industries, Jackson joined Essendon as its CEO in 1996.
Under his guidance, the Bombers became one of the richest clubs in the AFL, with net assets growing from $2.6m to over $19m.
But the latter period of Jackson's tenure, during which he held a board position, was controversial.
He was a key player in the decision to end Kevin Sheedy's 27-year reign as Essendon coach.
He also handed Sheedy's replacement, Matthew Knights, a contract extension that resulted in a big payout after Knights was sacked.
Since leaving the Bombers and being replaced by Ian Robson at the end of the 2009 season, Jackson has remained involved in football.
In 2011 he completed a review of grassroots footy for AFL Victoria, which has resulted in a major restructure of the way the game is administered at a local level.