The University of Oxford has become the first British university to top the Times Higher Education's global league table, knocking the California Institute of Technology into second place.
Oxford topped the list because it improved across the four main indicators that influence the rankings - teaching, research, citations and international outlook, Times Higher Education said.
But Britain's vote to leave the European Union could threaten the oldest university in the English-speaking world, locking academics out of research projects, said Phil Baty, the editor of the rankings.
"As well as some top academics reporting they have been frozen out of collaborative research projects with EU colleagues, many are admitting that they might look to relocate to a university outside the country," Baty told the BBC.
While Oxford, the University of Cambridge and London's Imperial College make the top 10 along with ETH Zurich, the list is dominated by US universities.
Stanford University is ranked third, the Massachusetts Institute of Technology fifth, Harvard sixth, Princeton seventh and the University of California, Berkeley and University of Chicago at tenth equal.
Cambridge was ranked fourth, Imperial eighth and ETH Zurich ninth.
More broadly, the rankings showed institutions in Asia had made progress with two new Asian universities now in the 100 and another four joining the top 200.