Fitzpatrick, 59, will take over from Brian Caldwell, who is joining Shrewsbury Town in the same role.
After two spells as a player in Paisley, during one of which the club won the 1987 Scottish Cup, Fitzpatrick moved into management at St Mirren.
He left in 1991 but returned five years later before having a brief spell as Clydebank caretaker boss.
The Scottish Championship club described Fitzpatrick on their website as having "been around the club for over 40 years in various roles".
And he said: "I am absolutely delighted to be back at St Mirren FC and look forward to the challenges ahead."
Chairman Stewart Gilmour added: "The board are delighted that Tony has accepted the position of CEO at the club.
"Tony has a wealth of experience in business as well as in football and we are sure he will be a huge asset to the club, the community and general wellbeing and future of St Mirren FC.
St Mirren also announced that chartered accountant Allan Gallacher will assist Fitzpatrick "in overseeing the financial side of the club".
Gallacher said he was "privileged and honoured" to take on his new role and Gilmour added: "We are also delighted to welcome Allan to the team, his financial expertise will be of great benefit to the club."
St Mirren have appointed former manager and player Tony Fitzpatrick as their new chief executive.