The former film director, who was behind the 'Death Wish' movies, has written, directed and starred in the insurer's advertising since October 2002 when the group shifted its creative in-house.
Winner has made Esure a household name and his phrase "calm down dear, it's only a commercial" a national catchphrase.
The new campaign, which remains in-house, will focus on the promotion of a rebranded Esure.com and features the Mister Mouse character that was introduced by Winner in the latest TV spots where the director plays himself and Mrs Winner.
The new icon is a "stop-motion" character, who will appear in television, press and poster ads from tomorrow May 25.
The Mister Mouse character, created in-house by Sian Vickers and Chris Wilkins with animation by Vinton Studios in the US, will "represent the internet age" and "is a fan of Esure rather than an employee of Esure".
However, Winner might well be back. Esure said that the move "doesn't signal an end to Winner" and that he continues to be involved with the brand.
"He will feature again and he also remains with us as an important adviser. However, for the moment, Mister Mouse is the right icon," Esure said.
Vickers and Wilkins worked with Peter Wood, who founded Direct Line Insurance, to create the Direct Line red phone in the 1980s.
Peter Wood, esure's chairman and group marketing director, said: "In developing a new icon for 21st century internet insurance I wanted to keep the directness of our Michael Winner approach while bringing to life the role of the computer mouse, which is, after all, the only tangible moving part in most e-commerce activity."
The campaign comes following research by the ICM Internet Shopping poll commissioned by esure, which found that people are three times more likely to shop for items using the internet than they are using the telephone.
Esure recently appointed Red Cell Response on a project basis for its £8m direct marketing account. Carat remains Esure's media agency and Carlson Digital in charge of online work.
Esure, which was founded by Wood as a joint venture with HBOS, has attracted more than 1m customers in four years and currently sells around 70% of policies online. The group is in the process of looking at loans and pet insurance for later in the year.
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