Mark Pritchard has resigned as deputy chairman of the Conservative Party International Office over David Cameron's approach to the European Union and other issues.
The Tory MP for The Wrekin said he had been "pondering this for about three or four weeks" and that the timing of the announcement was "purely coincidental".
The news came as Cameron faced questions from MPs in the Commons on last week's EU summit in Brussels, leading some to suspect the timing was deliberate.
Pritchard is a known eurosceptic and was among the Tory MPs that rebelled against the government by demandeding a referendum on Britain’s membership of the EU in the wake of the eurozone crisis.
In a letter to the prime minister seen by PoliticsHome, Pritchard said he could not continue in the post and speak out on issues as he wished.
"Given my concerns regarding an increasing number of government politics not least on immigration, Europe and a lack of clarity for national and individual aspiration, I believe remaining as deputy chairman would be inconsistent and inhibit my ability to speak out more rely on these and other issues," he said.
Pritchard is currently the secretary of the influential backbench Tory 1922 committee. The MP committed what was seen as career suicide in June 2011 when he said he had been "threatened" by Downing Street over his call for there to be a ban on wild animals being used in circuses.
Last week ministers indicated they would in fact introduce measures to ban circuses from using wild animals in their shows.
While he had not been afraid to speak out against the government previously, today's announcement indicates Pritchard is prepared to become more vocal in his opposition to some of the coalition's plans.