'Amazing journey': Wawrinka, 40, says farewell to Australian Open
The ninth seed from the United States sent the wildcard and popular former champion from Switzerland spinning out 7-6 (7/5), 2-6, 6-4, 6-4.
Wawrinka, who made his debut at Melbourne Park in 2006 and won the major in 2014, is playing his last season before retiring.
"I've had so many emotions here the last 20 years because of you guys," three-time Grand Slam winner Wawrinka told the crowd, who had roared him on throughout.
"It's been an amazing journey. I won my first Grand Slam here and I always enjoy being back.