Chelsea announced that Maresca and the club had "parted company" by mutual agreement as the Blues look to revive their season.
The 45-year-old Italian departs with Chelsea fifth in the Premier League, 15 points behind leaders Arsenal, having won just one of their last seven league matches.
In a club statement, Chelsea said: "During his time at the club, Enzo led the team to success in the UEFA Conference League and the FIFA Club World Cup. Those achievements will remain an important part of the club's recent history, and we thank him for his contributions to the club.
"With key objectives still to play for across four competitions including qualification for Champions League football, Enzo and the club believe a change gives the team the best chance of getting the season back on track. We wish Enzo well for the future."
Maresca's final match in charge was a 2-2 home draw with Bournemouth, extending a run of inconsistent results that intensified pressure on his position. He was absent from the post-match press conference, with the club attributing that to illness amid rising speculation about his future.
Chelsea now face a busy January schedule, starting with a trip to Manchester City in the Premier League. The club has yet to confirm who will take charge next, but a new head coach is expected to be announced in the coming days. Candidates reportedly include Strasbourg manager Liam Rosenior, among others.
Maresca leaves Stamford Bridge having lifted two trophies, the Conference League and the expanded Club World Cup, and having secured Champions League qualification last season, but results in the current campaign ultimately proved pivotal in the decision to move on.