The No. 92-ranked Hewitt, playing because of a tournament wild card, will hope to end an 11-match losing streak against top 10 opponents when he faces No. 7 Gilles Simon in the second round.
In blustery conditions, the 28-year-old Australian dropped serve five times but converted six of 11 break point opportunities on Sela's serve to seal the win in just under two hours.
The former Wimbledon and U.S. Open champion, a three-time semifinalist at Key Biscayne, slipped in the rankings last year after four months out for hip surgery and is hoping to improve his ranking significantly before Wimbledon this year.
Hewitt is on the bottom half of the draw with No. 2 Roger Federer, No. 3 Novak Djokovic and American Andy Roddick.
Four American qualifiers advanced to the second round: Taylor Dent beat Ricardo Mellow 6-1, 6-4; Robert Kendrick beat French veteran Arnaud Clement 6-3, 7-6 (5); Michael Russell overcame Victor Hanescu; and Kevin Kim progressed when Michael Llodra retired with a groin muscle injury after winning the first set 6-3.
Fabrice Santoro, the oldest player in the draw at 36 years, three months, was one of two Frenchmen to advance, beating Brazilian qualifier Thomaz Bellucci 6-4, 4-6, 6-1. Julien Benneteau had a 3-6, 6-3, 6-4 win over fellow Frenchman Florent Serra.
Marcos Baghdatis, who broke into the top 10 in 2006 after reaching the Australian Open final and the Wimbledon semifinals, had a 6-2, 6-2 win over Ernests Gulbis of Latvia.
On the women's side, Nicole Vaidisova of the Czech Republic beat Patricia Mayr of Austria 6-4, 6-2 and Slovakia's Daniela Hantuchova defeated American Melanie Oudin 4-6, 6-3, 6-2.
Jelena Dokic, a former Wimbledon semifinalist who returned to the top 100 - after a long climb back from a ranking in the 600s - after a surprising quarterfinal run at the Australian Open in January, beat Romania's Edina Gallovits 6-3, 7-6 (5).
Women's defending champion Serena Williams and the other seeded players received first-round byes and will be in action beginning Friday at the 12-day tournament.
Perhaps the foremost threat to Williams' reign at Key Biscayne is her sister, Venus Williams, a three-time champion seeded fifth. They could meet in the semifinals.
As usual, the sisters skipped the Indian Wells tournament this month, and they arrived at Key Biscayne following a monthlong layoff from the tour. Serena's focus is not yet entirely on tennis - she held a news conference Wednesday to introduce a new line of jewelry and handbags, discussing "price points'' and "comfortability'' with the same zeal she shows returning a second serve.
She said her passion for fashion provides a welcome diversion from tennis, but she finds it draining to be so busy between events.
"For me to play a tournament is the easiest thing in the world,'' she said. "It's like my relaxing time. If not, I'm busy doing a photo shoot, usually two a day. I have to practice really, really early, because I have to fit the other stuff in. Then I'm on the phone doing interviews - this is all in one day. I somehow have to go to the gym, and I don't know how I do it. It's really stressful and so much easier for me to play the tournaments.''
