Russian qualifier Andrej Rubljov, ranked 70th in the world, surprised everyone and defeated the Swiss World Tree in two straight sets 6-3, 6-4.
In the quarterfinals, it will be a Russian duel for Rubljov as compatriot Daniil Medvedev stands on the other side of the net.
Federer, 38, has not received a perfect upload for the US Open, which starts in just over a week. The Cincinnati tournament was his first after the loss to Novak Djokovic in Wimbledon in July and there were only two games for him.