Novak Djokovic was knocked out of the ATP Brisbane International in a stunning quarterfinal upset by World No. 293 Reilly Opelka in one hour and 40 minutes, in a late-night match on center court 7-6(6), 6-3.

The big-serving American hit 16 aces on the way to claiming the biggest victory of his career, in his first-ever match against the 24-time Grand Slam champion.

"The reality is we had nothing to lose coming in against him. He's the greatest player ever, so you end up playing more free and you take a lot more risks, because it's your only chance," Opelka said on court after the match. "If you play at your normal level, he's going to win every time."

The result leaves Djokovic stuck on 99 career singles titles heading into the Australian Open, which he has won a record 10 times.

Earlier, Belarusian world number one Aryna Sabalenka beat Marie Bouzkova of the Czech Republic 6-3, 6-4 to set up a semifinal showdown with Russian teen sensation Mirra Andreeva.