Cameron Norrie recovered from a sloppy start to earn a first career win over Andy Murray in their all-British clash and reach the Cincinnati third round.
Murray, 35, took advantage of errors from Norrie to win the first set, but faded late in the decider as the world number 11 completed the fightback.
Norrie will face Norway's Casper Ruud or American Ben Shelton in the last 16.
Norrie and Murray, who have regularly practised together and will be Davis Cup team-mates again next month, shared a warm embrace at the net after the left-hander clinched victory in two hours and 37 minutes with a forehand winner.