Tony Collins, who has been with the firm for 14 years and served as chief executive for nine years, will stay on as a consultant to advise Virgin on its franchise bids.
Chief operating officer Chris Gibb is also stepping down after a decade with the company, which is co-owned by Virgin Group and Stagecoach.
The retirements have sparked a unusual reshuffle that will place joint executive chairmen Patrick McCall and Martin Griffiths at the helm of a new exec team, with finance director Phil Whittingham also taking on more responsibility.
“Tony has been a wonderful leader of Virgin Trains over the past nine years, spearheading the development of a world-leading railway which is loved by its customers,” said Virgin Group president Sir Richard Branson.
“Tony, Chris and the team at Virgin Trains have transformed the West Coast Main Line from a laughing stock into Europe’s busiest long distance rail service.”
Virgin Trains is running the West Coast Main Line on a short-term contract extension while the government restarts its franchise contests.
The route, which had been awarded to First Group for 23 years before the process collapsed last year, will be assigned its next operator by 2017.
Virgin is also interested in taking on the East Coast Main Line, which is currently run by the state.