The last female-only college outside Oxbridge will accept men from next year in a move described by its principal as "sad and historic".
Durham University said the decision to admit men to St Mary's College had been taken by the governing council after an analysis of its dwindling market share.
Despite strenuous efforts to attract students, the demand for places at the college, which overlooks Durham Cathedral, has remained small, against a background of rising applications to the university.
This year, only 194 of the 20,000 applicants specifying a first-choice college selected St Mary's.
College principal Jenny Hobbs said she accepted that the market for female-only colleges was no longer viable.
She said: "We can't keep on offering something that only a minority of students wants, and I accept the university's decision.
"But I am saddened and concerned about the issue of looking after the interests of an important minority of students who for different reasons - some religious, some cultural - have sought out a single-sex college. They will have nowhere to go."
Ms Hobbs said St Mary's, which houses 700 students, attracted a high proportion of students from ethnic minorities.
She said that the university had agreed to continue to offer areas of single-sex accommodation, which was an important concession.
But she added: "I can't help feeling that as long as there is a glass ceiling, we will need women's colleges, so now we have to find a way of creating opportunities for women seeking leadership roles."
Sir Kenneth Calman, vice-chancellor of Durham, said the university recognised the strengths of St Mary's active student community and its broad range of backgrounds.
"These are the qualities we wish to build on to provide an even-stronger student experience to the growing number of applicants to the university in the future," he said.
"We believe the time is now right to open up the college to both men and women."
A referendum within the college found more than 60 per cent of students were in favour of admitting men.
Haley O'Connor, president of St Mary's junior common room, said that the college's segregated ethos no longer fitted the modern world.
"There has been a perception that the college is a second-rate choice, a kind of nunnery on a hill, but this is completely misguided and it can be a very positive place to study," she said.