Venus, 33, appeared to be regaining her form after reaching the final in Auckland to start off the 2014 season. She had been dealing with various injuries and an illness in recent years.
“The last 12 months I have had issues, but this year I definitely am looking forward to having a good run and feeling well,” she said (via Associated Press).
But against Russia’s Ekaterina Makarova, the seven-time Grand Slam champion struggled with her serve and committed a slew of errors – she had 56 unforced errors – to fall 2-6, 6-4, 6-4.
Makarova, 25, reached her first quarterfinal at a major last year at the Australian Open when she upset Serena in the round of 16.
The top-seeded Serena, 32, was in dominant form, beating Australian wild-card Ashleigh Barty, 6-2, 6-1, in just 57 minutes.
“You have to be ready,” Williams said of the 17-year-old Barty (via Associated Press). “She had nothing to lose.”
Serena has now won 23 consecutive matches – including 18 from last season and a title at the Brisbane International earlier this month.
Serena plays Serbian Vesna Dolonc in the next round.
- No. 1 Serena Williams (USA) def. Ashleigh Barty (AUS), 6-2, 6-1
- No. 22 Ekaterina Makarova (RUS) def. Venus Williams (USA), 2-6, 6-4, 6-4
- Lauren Davis (USA) def. Sachia Vickery (USA), 6-3, 6-3
- Irina Falconi (USA) def. Anabel Medina Garrigues (ESP), 6-3, 6-1
- Alison Riske (USA) def. No. 23 Elena Vesnina (RUS), 6-2, 6-2
- Madison Keys (USA) def. Patricia Mayr-Achleitner (AUT), 6-2, 6-7 (8), 9-7
- Sam Querrey (USA) def. Santiago Giraldo (COL), 6-3, 6-3, 3-6, 7-6 (3)
- Adrian Mannarino (FRA) def. Steve Johnson (USA), 3-6, 6-3, 6-0, 5-7, 6-4
- No. 30 Dimitry Tursunov (RUS) def. Michael Russell (USA), 6-2, 6-2, 6-3
- Florian Mayer (GER) def. Denis Kudla (USA), 6-4, 6-2, 6-4