He had been in charge of the Welsh side since April 2004, but leaves on the back of three successive losses.
Saturday's home defeat at the hand of table-topping Oldham saw the Swans drop out of the play-off positions.
Jackett becomes the second League One manager this week to lose his job - after Colin Todd was sacked as Bradford City boss on Monday.
"It is with great regret that Swansea City must announce that the contract of manager Kenny Jackett has been terminated by mutual agreement," read a statement from the Welsh club.
"After a full and frank discussion between Kenny and chairman Huw Jenkins on Monday afternoon, the club felt that Kenny was the best person to reverse the recent slump in form.
"However, after thinking long and hard about the situation over the past 48 hours, Kenny has reluctantly come to the conclusion that the time is right for him and the club to make a clean break."