With the temperatures again sizzling around 33 Celsius (93 Fahrenheit) at Melbourne Park, the American 18-time Grand Slam champion took time to adjust to the sauna-like conditions against Russian veteran Vera Zvonareva.
She had to save two set points before exploding into action in the second set to easily win 7-5, 6-0 and keep alive her dream of a sixth Australian title.
Djokovic, gunning to be crowned champion a fifth time, was on fire in his showdown against Andrey Kuznetsov, crushing the hapless Russian 6-0, 6-1, 6-4, while defending champion Stan Wawrinka had to work hard to get past Marius Copil.
In a blockbuster evening clash, two-time champion Azarenka crushed close friend and eighth seed Caroline Wozniacki 6-4, 6-2 as her comeback from injury gathers steam.
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Williams said she only started finding her range when she relaxed.
"She started out really well, she was really aggressive and I was a little too passive," said Williams, the top seed.
"Once I got down I thought 'Serena, you've done so well here you've got nothing to lose, just have fun and enjoy yourself' -- then I started to play a lot better."
Sixth seed Agnieszka Radwanska is also in ominous form after hiring former great Martina Navratilova as her coach.
The Pole, a semi-finalist last year, took just 44 minutes to brush aside Sweden's Johanna Larsson 6-0, 6-1 and has only lost four games in two matches.
"She's helped me a lot, on and off the court," Radwanska said of Navratilova.