With the temperatures again sizzling around 33 Celsius 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.
Serena said she only started finding her range when she relaxed. "She [Zvonareva] started out really well, she was really aggressive and I was a little too passive," said 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."
While the old guard of Serena and Maria Sharapova are safely into the third round, the new generation of Eugenie Bouchard and Simona Halep have looked more impressive in the early rounds.
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.
Serena faces a tricky third round match against another of the new young guns in Spanish world number 24 Garbine Muguruza, who beat Daniela Hantuchova 6-1, 0-6, 6-1.
Her sister Venus also progressed, as did Czech fourth seed Petra Kvitova.
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.
Azarenka, ranked just 44 after an injury-marred 2014, again showed why she is the most dangerous unseeded player at this year's tournament after upsetting Wozniacki. The win keeps her on track to meet Serena in the quarter-finals.
Djokovic, Wawrinka, Nishikori also through
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.
The Romanian took the fourth seed to two tiebreakers before the Swiss star triumphed 7-6 (7/4), 7-6 (7/4), 6-3.
"The court was quite fast and he was really aggressive on serve and I was happy to get through in three sets," said Wawrinka.
Fifth seed Kei Nishikori was forced to four sets by Croatia's Ivan Dodig, digging deep to keep his dream of a maiden major title alive with a 4-6, 7-5, 6-2, 7-6 (7/0) win in front of a noisy pro-Japanese crowd.
Others who progressed in Melbourne included Canadian eighth seed Milos Raonic, Spain's ninth seed David Ferrer and 12th seeded compatriot Feliciano Lopez.
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