Hours earlier, across the way at Louis Armstrong Stadium, Venus Williams did her part with another straight-set victory, eliminating 40th-ranked Camila Giorgi of Italy, 6-4, 7-5.
"Normally I say cheer for me, but I say cheer for who you want, me or Venus", said Serena, laughing, according to USA Today. Venus won that one. "She was playing really well, she'd played four matches already, she was used to the conditions".
The 25-year-old eventually closed out the set and, despite going a break down in the first game of the decider, proved too strong for the 21-year-old Ukrainian, who was playing in the main draw of a Grand Slam for the first time.
"The last time we played in Australia it was two against one so this time it will be fair", joked Venus of her most recent meeting with her sister at the 2017 Australian Open, when Serena won the title despite being in the early stages of pregnancy.
Defending champion Sloane Stephens avoided an early exit, recovering from a set down to defeat Ukrainian qualifier Anhelina Kalinina 4-6 7-5 6-2.
Azarenka was among the first players to condemn the United States Tennis Association (USTA) for handing French player Alize Cornet a code violation for changing her shirt on court on Tuesday.
The former World number one came to the French open rocking a lifesaving body compression catsuit - one which the French Tennis Federation banned citing indecency and "respect" for the tournament. "I feel like if and when, or if they know that some things are for health reasons, then there's no way they wouldn't be ok with it".
Meanwhile, Ukrainian seventh seed Elina Svitolina also progressed with a 6-2 6-3 win over Germany's Tatjana Maria.
"I pretty much have a clue [who I could play in the next round]", Venus Williams said.