Rowan Alexander will not be at the helm when Gretna kick off their first season in the SPL on 4 August.
Irons will lead Gretna in their first season in the top flight
Assistant manager Davie Irons will step up, with Derek Collins acting as his number two, BBC Sport understands.
Irons led Gretna to a third successive promotion when Alexander was given time off for health reasons in March.
Alexander, who signed a five-year rolling contract in May 2006 along with Irons, had said that he hoped to return to his post after the summer.
A compensation agreement is currently being thrashed out with Alexander, who joined Gretna in 2000.
He was in charge when the Black & Whites secured their place among the ranks of senior Scottish clubs in 2002.
And Alexander went on to win the Division Three and Two titles, as well as steering the club to the Scottish Cup final in 2006.
Meanwhile, Gretna captain Chris Innes is confident he and his team-mates will hold their own in the top flight.
"We're under no illusions but to go in with a negative attitude to start with is not the best idea, so we need belief," he told BBC Sport.
"I think we will be in the SPL at the end of the season.
"Consolidation is the priority but that is not to say we want to finish 11th.
"We want a mid-table finish which would be a fantastic achievement for a club of this size and our experience."
Midfielders Paul Murray and Abdul Osman have been signed up for the new campaign and more fresh faces will follow.
"We need to strengthen the squad and get a good blend," added former Kilmarnock and Dundee United defender Innes.
"We have a lot of positives to take from the last few years and this is where we want to be.
"We are now up against the best and it's quite surreal that Gretna are here in the sense that it's taken me personally three years to come back from where I left and it's a challenge I'm relishing."
Finally, Innes was full of praise for both Irons and Alexander, saying: "Davie has handled the situation exceptionally well and is a credit to the club and his family.
"But Rowan put in a hell of a lot of work before that."