Lee, director of comms and public affairs for London 2012 and the interim London Organising Committee of the Olympic Games (Locog), will leave on 30 November.
Lee - voted PRWeek's PR Professional of the Year just a fortnight ago - is understood to be setting up his own consultancy providing counsel to bodies that are pitching to host major sports events. He is said to have been approached by a number of organisations, but has decided to stay independent.
His previous work for Uefa and leading politicians would make him a prime target for communicating an English bid for the 2014 or 2018 World Cups, although the Football Association has not yet decided for which of these it will bid.
Lee joined the London 2012 team at the end of 2003 and worked closely with bid chairman Lord Coe and its CEO Keith Mills. He had formerly worked at organisations including the Premier League and Westminster Strategy.
Coe said in a statement, released on 1 November: 'Mike has made a fantastic contribution to London 2012, particularly in positioning and communicating our plans to key audiences, including the media.'
He added: 'He thoroughly deserves his recent accolade as PR Professional of the Year. I wish him well in all that he plans to do in the future.'
Mills, meanwhile, described Lee as a 'key member' of the successful bid team. Mills added: 'He has left basis for a strong communications platform for the next seven years.'
Lee himself said: 'Wining [the bid] was professionally my proudest moment.'
Jackie Brock-Doyle, currently head of PR and media, will take responsibility for the director of comms role from December.