The former Rangers and Scotland skipper resigned in the wake of the Bully Wee’s 1-0 defeat at Annan Athletic on Saturday.
The defeat left Clyde - pre-season promotion favourites - languishing in eighth place in the League Two table.
Since beating Berwick Rangers 3-2 at Broadwood in November Clyde have taken just two points from 10 games, both from goalless draws with league new boys Edinburgh City.
The Bully Wee did make it to the last 16 of the Scottish Cup and were unlucky to lose to Championship side Ayr United, who snatrched a last-gasp extra-time winner at Broadwood.
But in the end the club’s league position wasn’t good enough with Saturday’s defeat at Annan - a match labelled by Ferguson as “must win” beforehand - proving the final straw.
A club statement said: “The Board has today reluctantly accepted the resignation of first team manager, Barry Ferguson.
“Despite a welcome run in the William Hill Scottish Cup, which ended with an agonising defeat to Championship side Ayr United in a fifth round replay, both the manager and the club were disappointed with the recent poor run of League results, often not reflecting the effort and standard of play, which culminated in the defeat at Annan yesterday.
“That result leaves the club with only an outside chance of achieving the objective of securing a play-off place and then promotion to League 1.
“The club would like to thank Barry for his unstinting commitment to the job over the last two and a half years and wishes him every success in the future.”
Ferguson said: “I want to wish the club all the very best in the future. I hope that it can go on and achieve its aim of reaching the play-offs this season.”
Clyde’s next game is against Montrose at Broadwood on Tuesday night.