No. 2-seeded Maria Sharapova overcame 12 double faults and erased 10 break points to rally past Shahar Peer of Israel 4-6, 6-3, 6-3, while No. 4 Caroline Wozniacki beat Barbora Zahlavova Strycova 6-4, 6-0.
Two-time champion Kim Clijsters defeated No. 14-seeded Julia Goerges of Germany 6-2, 7-5. No. 13 Jelena Jankovic lost her opening match to Mona Barthel of Germany 6-0, 6-3.
U.S. Open champion Sam Stosur beat Russian qualifier Valeria Savinykh 6-4, 6-0 and American qualifier Sloane Stephens ousted No. 30 Sara Errani 3-6, 6-2, 7-5.
Williams' victory also marked her first match at Key Biscayne since she lost to Victoria Azarenka in the final three years ago.
“I was really nervous out there,” Williams said. “I haven't played here for so long, and I wanted to do well. My worst fear actually was as long as I don't hit a ball in the stands, I'll be good. I didn't do that today, so it worked out well for me.”
Williams looked right at home, and not just because her purple dress matched the color of the court. The five-time champion lives two hours up Interstate 95 in Palm Beach Gardens.
Health issues prevented Williams from playing at Key Biscayne in 2010 and 2011, and a left ankle injury has slowed her this year. Aside from two Fed Cup victories in February, she was playing for the first time since she lost in the fourth round at the Australian Open.
Williams, who received a first-round bye because she's seeded 10th, looked fit but rusty and endured some sloppy moments. At one juncture she froze in a pose behind the baseline, hands on her hips as she fumed after making a flurry of mistakes.
“I got a little frustrated,” she said. “My frustration is more like a motivation frustration, so it helps me.” While her returns were especially erratic, she served six aces and lost only seven of 34 points on her first serve.
Williams said she found her older sister's first-round victory inspiring. Venus was diagnosed last summer with a fatigue-causing autoimmune disease, and Serena has tried to help her sister adjust to a restricted diet by keeping unhealthy food out of the kitchen.
Best friends since childhood, the sisters continue to share a home as celebrity millionaire adults, and Serena laughed when asked about the arrangement.
“Yeah, we probably should have moved out a long time ago,” she said. “Honestly, it's ridiculous now, like we have kind of held each other back.
“Hey, we're in for the long run. That's like my husband. We're always laughing together. You know, I tell her everything, so it's fun.”
American Ryan Harrison, a wild card entry, rallied past Polito Starace of Italy 6-7 (6), 6-4, 6-4 and will next face two-time champion Roger Federer. The match will be a gauge of progress for the 19-year-old Harrison, who is ranked 73rd but has yet to beat a top-10 player.
“He's very talented,” Federer said, “and I'm sure he's going to be making his move up the rankings very easily this year and in the coming years. He has a big game.”