Mr Thomas, 39, is replaced by Ian Lenagan, the club’s owner, who becomes the new executive chairman.
Mr Lenagan, who is also the chairman of Wigan Rugby League Club, immediately set his sights on working with manager Chris Wilder to lead the club to promotion this season.
His company, Woodstock Partners, bought United for £1 from Firoz Kassam in 2006, but after suffering relegation, the club was in a poor state when Mr Thomas became chairman on October 2, 2008.
United were 19th in the Blue Square Conference, attracting an average crowd of 4,000 for home games, and battling crippling debts that had left the club on the brink of administration.
However, together with Mr Wilder, Mr Thomas led the team to promotion back into the Football League. Last season the U’s finish ed ninth in npower League Two.
“I look back with an immense amount of pride,” Thomas said.
“It has been a challenging, but a great experience and I’m proud that I feel I have made some real improvements.
“Our reputation in and around Oxfordshire has changed dramatically – I think people are very proud to be associated with the football club now.”
Winning the Conference play-off final at Wembley two years ago was the obvious highlight, but Mr Thomas said there were other special memories.
“The Wembley week was just an amazing time, as were the big games against Swindon last season and West Ham in the Carling Cup,” he added.
“But walking around the pitch here with Charlotte Nott at the Rotherham game last season, that was a massive highlight for me, as were the military days and open days that I introduced.”
Mr Thomas will now weigh up his options before deciding on his next move.
“Someone has asked me about a potential opportunity in the Middle East and there’s some stuff in the US that’s interesting, so I will take my time and just see what emerges,” he said.
Mr Lenagan praised the work of Mr Thomas during his four years at the Kassam Stadium.
“Since selling my main software business, Workplace Systems, at the end of last year, I now have more time available and have been taking a more hands-on involvement in Oxford United. This move is a natural progression.”
He added: “When I appointed Kelvin, the club was in a poor state across many areas and it is largely down to his efforts that Oxford United is in a better position now.”