Johnson won just seven of his 34 games in charge at Northampton and the club is currently four places from the bottom of League Two.
“Gary has been a successful manager in the past and I am sure he will be again in the future,” Northampton chairman David Cardoza said.
“Unfortunately, things just haven’t worked out for Gary here, and there comes a point when you have to accept that fact, take stock and make a decision and following a discussion between Gary and I over the weekend, it was decided that we part company.
“We wish Gary all the very best for the future. We part on good terms and our search for a new manager now begins.”
Johsnon added: “After discussions with the Chairman, it was agreed that I part company with the club.
“I would like to thank the Chairman for his support during my time here. I am sorry we did not reach the expectations we had set ourselves but I wish the club, it’s players and supporters all the very best for the future.”