Brent Hoberman announced that he will take up the role of part-time chairman of the company that he set up with Martha Lane Fox eight years ago.
He will be succeeded as chief executive by Ian McCaig, who was appointed as chief operating officer in 2003 and was responsible for the group's operations throughout Europe.
In a statement, Mr Hoberman said a part-time role would enable him to spend more time on other business projects.
He said: "Since I co-founded lastminute.com in 1998 I haven't seen much daylight and I feel it's time to broaden out a little."
Mr McCaig, 40, takes over at a time when the travel industry looks set for a new round of consolidation and opportunities are appearing as consumers rethink how they book overseas holidays and hotel rooms.
Sabre - the parent company of Travelocity - paid é577m for lastminute a year ago to accelerate its expansion beyond basic air travel. As well as flights and holidays, lastminute's reach includes entertainment tickets and restaurant bookings.
The deal brought windfalls totalling é40m for Mr Hoberman and Ms Lane Fox, who ended her daily involvement with lastminute in November 2003 and was then badly injured in a car crash in Morocco six months later. Mr Hoberman owned 4.6 per cent of shares and netted é26.9m when the 165p-a-share deal went through last year.
He said: "I'm passionate about lastminute.com and its future success and I believe my role as chairman will enable me to take a better perspective of the business."
At the time of its flotation in 2000, lastminute was valued at more than many mainstream retailers, even though it had turnover of less than é4m.
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