The four-time Aussie titlist Djokovic won the first nine games and needed just 84 minutes to dispose of Russian Andrey Kuznetsov 6-0, 6-1, 6-4 at Rod Laver Arena.
"Overall I executed the game plan," said Djokovic. "Everything I intended to do, almost 100 percent, from every second in my game, serve, baseline play, aggressive shots and aggressive returns."
"He [Kuznetsov] dropped his first-serve percentage a lot in the second set and obviously allowed me to have a lot of looks at the second serves. That, as well, gave me an opportunity to step in and just swing through the ball."
The reigning Wimbledon champion Djokovic captured three straight Aussie crowns from 2011-13.
His next step toward becoming the second man to win five Aussie Open titles will come Saturday against 31st-seeded Spaniard Fernando Verdasco, who handled Japan's Go Soeda 6-3, 6-2, 7-6 (7-3) at Melbourne Park.
The fourth-seeded Wawrinka extended his winning streak at this major to nine with a 7-6 (7-4), 7-6 (7-4), 6-3 win over Romanian qualifier Marius Copil. The tight affair saw the champ win just four more points than the game Copil, playing in his first Grand Slam main draw.
"It was quite a tough match," said Wawrinka. "Happy to get through, especially in three sets. Condition wasn't easy today. Quite hot, really fast on the court, and he was playing great. He was serving big, putting lots of pressure. Wasn't playing my best tennis, but I'm happy the way I fight today."
Wawrinka has reached the third round in Melbourne seven years running. His next opponent will be Finnish left-hander Jarkko Nieminen.
Fifth-seeded Kei Nishikori fell behind early against Croat Ivan Dodig, but wound up pulling out a 4-6, 7-5, 6-2, 7-6 (7-0) victory, while eighth-seeded Canadian Milos Raonic topped American Donald Young 6-4, 7-6 (7-3), 6-3 and ninth-seeded former French Open runner-up David Ferrer overcame Ukrainian Sergiy Stakhovsky 5-7, 6-3, 6-4, 6-2.
Feliciano Lopez, seeded 12th, trailed by two sets to Frenchman Adrian Mannarino, staved off a match point in the third and advanced when Mannarino retired due to heat exhaustion in the fourth. Lopez was leading 4-0 in the fourth prior to Mannarino calling it quits, as Lopez moved on in 4-6, 4-6, 7-6 (7-3), 4-0 fashion.
American John Isner reached the round of 32 with a 6-4, 7-6 (7-4), 4-6, 6-4 decision over Austrian Andreas Haider-Maurer. The 19th-seeded Isner avoided a date with No. 13 Roberto Bautista Agut, who was ousted by Luxembourg's Gilles Muller 7-6 (7-5), 1-6, 7-5, 6-1 on Day 4.
In other second-round action involving seeds, 6-foot-8 Pole Jerzy Janowicz upended No. 17 Frenchman Gael Monfils 6-4, 1-6, 6-7 (3-7), 6-3, 6-3, No. 18 Frenchman Gilles Simon bested Spaniard Marcel Granollers 7-6 (7-5), 6-2, 6-4, and American Steve Johnson pulled off a mild upset with a 6-3, 6-4, 6-2 pasting of No. 30 Colombian Santiago Giraldo. Johnson will next square off against Nishikori, last year's U.S. Open runner-up.
Also on Thursday, Nieminen doused German Matthias Bachinger 7-6 (7-4), 7-5, 7-5; Canada's Vasek Pospisil overcame Italian Paolo Lorenzi 6-7 (3-7), 7-6 (7-4), 6-3, 6-4; Spaniard Guillermo Garcia-Lopez bested Colombian Alejandro Gonzalez 6-1, 6-3, 6-3; and German Benjamin Becker came all the way back to dismiss long-time Aussie favorite Lleyton Hewitt 2-6, 1-6, 6-3, 6-4, 6-2. The 33-year-old former world No. 1 Hewitt is a two-time Grand Slam champion and former Aussie Open runner-up. Becker should have his hands full with the big- serving Raonic on Saturday.
The third round will get underway Friday, as second-seeded former world No. 1 Roger Federer will face Italian Andreas Seppi, third-seeded former top-ranked star Rafael Nadal will battle Israeli Dudi Sela and sixth-seeded three-time Aussie Open runner-up Andy Murray will tangle with Portuguese Joao Sousa.
Federer owns 17 a men's-record major titles, including four at the Aussie Open. The 14-time Grand Slam winner and reigning French Open king Nadal beat Federer in the 2009 final and is a two-time runner-up here, including last year when he was stunned by Wawrinka in the finale.
Also on Day 5, seventh-seeded former Wimbledon runner-up Tomas Berdych will take on Serb Viktor Troicki and 10th-seeded Bulgarian Grigor Dimitrov will be opposed by former Melbourne runner-up Marcos Baghdatis.