Playing her first tennis in seven studded Sony Ericsson Open.
The 10th-seeded Williams waltzed past Chinese wild card Zhang Shuai 6-2, 6-3 in 1 hour, 20 minutes on the hardcourts at the Tennis Center at Crandon Park.
The Florida resident and former world No. 1 Williams, who lives in Palm Beach Gardens, is a five-time Miami champ (2002-04, 2007-08) and two-time runner-up. Last year's U.S. Open runner-up will meet Italian Roberta Vinci in the round of 32 here.
Second-seeded Russian Maria Sharapova also advanced on Thursday, overcoming a shaky start and 11 double-faults -- seven in the first set alone -- to take down Shahar Peer of Israel 4-6, 6-3, 6-3.
Sharapova was last week's Indian Wells runner-up to Victoria Azarenka, who also topped Sharapova in last year's finale here in Miami. The three-time major champion and former world No. 1 Sharapova is 0-3 in three Miami finals.
Another former world No. 1, Caroline Wozniacki, also moved on, albeit in much simpler fashion. The 21-year-old Dane, seeded fourth here, routed Czech Barbora Zahlavova Strycov 6-4, 6-0.
Meanwhile, another former top-ranked star, Kim Clijsters, posted her second win in two days with a 6-2, 7-5 ousting of 14th-seeded German Julia Goerges.
The oft-injured 28-year-old Clijsters, playing her first tennis since the Australian Open in January, is a four-time major champion and was a Miami titlist in 2005 and 2010.
Sixth-seeded U.S. Open champion Samantha Stosur reached the round of 32 with a 6-4, 6-0 victory over Russian qualifier Valeria Savinykh, and eight-seeded French Open titlist Li Na of China joined her with a 7-5, 6-2 win over Hungarian Melinda Czink.
In other action involving top-16 seeds, No. 12 German Sabine Lisicki leveled Swede Sofia Arvidsson 6-3, 6-2 and rising German Mona Barthel bounced No. 13 Serb Jelena Jankovic 6-0, 6-3. The former world No. 1 Jankovic, the Sony Ericsson runner-up in 2008, has now lost her last three matches overall, including her opener at Indian Wells two weeks ago.
Czech lefthander Iveta Benesova outlasted 26th-seeded fading Russian Svetlana Kuznetsova 1-6, 7-6 (9-7), 7-6 (9-7) in 2 hours, 51 minutes. The two-time Grand Slam champion Kuznetsova titled here back in 2006.
No. 17 Chinese Peng Shuai blasted French qualifier Stephanie Foretz Gacon 6-1, 6-2; Russian Ekaterina Makarova erased 19th-seeded Russian Anastasia Pavlyuchenkova 6-1, 6-2; a 21st-seeded Roberta Vinci moved on with a 7-5, 6-1 victory over Bulgarian Tsvetana Pironkova; 23rd-seeded Belgian Yanina Wickmayer dismissed New Zealand's Marina Erakovic 6-3, 6-4; and South African Chanelle Scheepers doused 25th-seeded Spaniard Anabel Medina Garrigues 1-6, 6-4, 6-0.
Finally, 29th-seeded Czech ousted American Christina McHale 0-6, 7-5, 6-1, while American Sloane Stephens rolled over 30th-seeded Italian Sara Errani 3-6, 6-2, 7-5.
The winner of the $4.828 million tournament will collect $712,000.