Djokovic beat Gael Monfils in a four-set match in which both players slouched and crouched over in the shade at the back of the court as the temperature reached 104 degrees Fahrenheit.
The 4-6, 6-3, 6-1, 6-3 win was a relief for Djokovic, who says he's still not 100 percent after six months off the tour with an injured right elbow and who lost in a second-round shocker here last year.
Now seeded 14th, Djokovic needed four match points in an eight-minute last game before clinching the win -- his 15th straight against Monfils.
"It was obvious we both suffered on the court today,'' Djokovic said. "Really tough conditions -- brutal.''
Monfils said afterward that "it was tough to breathe." He was checked by a tournament doctor during the second set.
"I get super dizzy. I think I have a small heat stroke for 40 minutes," Monfils said. "Couldn't feel fresh. I try to cool down. But even with the ice towel, the water, I think my body was super warm. Could not, you know, be very fresh after any points, so it was tougher."
Djokovic noticed Monfils was struggling.
"It was obvious that he was not at his best. ... At times we were both just trying to get a little bit of extra breath, a few seconds more, so we can recover," he said. "We were also getting into some long exchanges and rallies. That's what happens when we play each other."
It's supposed to be even hotter on Friday, with a forecast high of 42 Celsius (108 Fahrenheit).
Djokovic was asked if play should continue in such heat.
"I think, you know, there are certain days where you just have to, as a tournament supervisor, recognize that you might need to give players few extra hours until it comes down," he said. "I understand there is a factor of tickets. If you don't play matches, people will be unhappy. You have to take into consideration different angles before making a big call like that.
"But, you know, people might say, Well, at this level you have to be as a professional tennis player fit. It's the beginning of the season. You kind of work and train hard to be able to sustain these kind of conditions, to be tough. But I think there is a limit, and that is a level of I guess tolerance between being fit and being, I think, in danger in terms of health."
Djokovic said that his match was right at the limit.
"But it's our choice, at the same time, whether we want to play or not," he said. "So I don't want to sound ungrateful. In contrary, I'm very grateful. But I also think that there should be some kind of rational conversations about, you know, rules that are maybe imposed or certain things that are concerning players' well-being."
Wawrinka wasn't sure if he was ready to play the Australian Open after left knee surgery last year put him behind in his preparations. It showed on Thursday.
Wawrinka never looked capable of winning his third-round match, losing 6-2, 6-1, 6-4 to American Tennys Sandgren. The Swiss star is ranked and seeded ninth; Sandgren is 97th.
The 2014 Australian Open champion spent eight weeks on crutches following his surgery, and he pulled out of an exhibition tournament in Abu Dhabi two weeks before the Australian Open.
He admitted that he waited until the last possible moment before deciding to play in Melbourne after not having played a competitive match since Wimbledon.
Wawrinka, 32, was attempting to make the third round for the 10th consecutive year.
Under the lights at Rod Laver Arena, Federer's match was a little cooler. He beat Jan-Lennard Struff 6-4, 6-4, 7-6 (4).
Federer maintained his record of always reaching the third round at Melbourne Park, and this is his 19th appearance. Five of his 19 Grand Slam singles titles have been in Australia.
Despite his straight-sets win, Federer was only able to convert three of his 11 break-point chances, and only one of six in the third set.
Federer, 36, will next play French veteran Richard Gasquet, who is 31. Federer has beaten Gasquet 16 of the 18 times they've played.
It's the second year in a row that Zverev has reached the third round. Last year, the 20-year-old German who is predicted to be a Grand Slam winner lost to eventual runner-up Rafael Nadal in five sets.
Zverev won five titles last year, including Masters 1000 titles at Rome and Montreal.
The fifth-seeded Austrian improved his five-set record at Grand Slams to 3-3 with the win. He lost both five-setters that he played last year at the majors to Tomas Berdych at Wimbledon and to Juan Martin del Potro at the US Open.
Thiem counted 21 aces among his 57 winners in the match with Kudla. Thiem was broken three times in the opening set and once in the second set, then didn't face another break point for the rest of the match.
It was only the second time in the now-59th-ranked Benneteau's career -- in 19 attempts -- that he's managed to beat a player in the top 10 in a Grand Slam singles match.
The 13th-seeded Querrey was one of 10 American players -- men and women -- to reach the second round from the 32 who started the main draws, the lowest number of Americans through to the second round in Melbourne since seven in 2011.
The Associated Press contributed to this report.