The three-time Grand Slam winner had a mid-match wobble before eliminating Lithuania's Ricardas Berankis 6-3, 6-4, 2- 6, 7-6 (7/2) in 2hr 47min on Hisense Arena.
It was a confidence booster for the 2014 Melbourne Park champion, who had a troubled lead-in to the year's opening Grand Slam, pulling out of an exhibition event in Abu Dhabi on his way to Australia.
The Swiss star, who defeated Rafael Nadal to win the 2014 Australian Open, has slipped to nine in the world rankings, having not played since his first-round Wimbledon loss to Russian Daniil Medvedev six months ago.
"It's great to be back. It's great to win, for sure," he said.
"It was a tough one in all aspects of the game, but in general, I'm really happy to get through a match like that, to fight the way I did today, to win the match like this."
Wawrinka admitted he was still experiencing pain but was relieved his knee had stood up to the physical demands.
"I still have some pain. It depends the way I'm moving, how I push on it," he said.
"The knee didn't move even after three hours, so that's great."
The Swiss star, who next plays American Tennys Sandgren, said his plan was to keep going as far as he can to raise his fitness levels.
"I don't think I will change much. The plan is to play a bit more if the knee is keeping (together) because I didn't play for six months," he said.
"First was to come here, see if I was able to play. I won the first match. I'm going to focus on the tournament.
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