At a heated meeting of the University of Leeds senate on 6 July, academics backed a motion condemning the universities and science minister's handling of higher education reforms.
The vote of no confidence was won narrowly by Mr Willetts' critics, although many senate members abstained.
Leeds is the second university to publicly and officially condemn the government's higher education reforms, after Oxford dons delivered a crushing motion of no confidence at a congregation meeting on 2 June.
Mark Sewards, communications officer for Leeds University Union, who attended the meeting, said: "There was a lot of anger - it was clear that they were not happy with the measures announced in the White Paper.
"There were many abstentions and even those who voted against the motion said they were unhappy about what was happening. They were just concerned if it was the right time and place to pass a motion."
David Barclay, president of the Oxford University Student Union and founding member of the No Confidence Campaign, said the decision was "a huge step forward in the fight-back against the government's disastrous plans for universities".
He added: "This brave decision by Leeds is the first of what will be a long line of blows to the government's vapid and dangerous White Paper.
"Students do not want to be consumers, and academics do not want to see the universities they love condemned to underfunding and the whims of the market."