With plenty of backing from the South Florida crowd, Nadal never looked in trouble against the 83rd ranked Sela as he ran out 6-3, 6-4 winner in one hour and 20 minutes.
Rain delays earlier in the day pushed back Nadal's appearance on court and gusty conditions also made it tricky for the former world number one.
"It has been very tough and long day for everyone I think. Rain delay a couple of times and then the wind was very, very high," he said.
The Spaniard is looking to win his first Miami title after losing in the final four times in his career.
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"I was close enough four times in my career. I am going to try to give myself more chances during this year and during the next couple years. But this tournament is a tough tournament and anything can happen," he added.
Second-seed Nishikori beat big-serving South African Kevin Anderson 6-4, 6-3 on center court and will face Fernando Verdasco of Spain or young American Ernesto Escobedo in the next round.
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The Japanese, beaten by Novak Djokovic in last year's Miami final, didn't face a break point in the contest and won 88 per cent of his first-serve points.
Nishikori, 27, said he was looking to make a breakthrough in one of the slams this year and believes a win in Miami could give him the boost in belief that he needs.
"I think if I can win big tournaments like this or some Masters, that's going to give me a lot of confidence for sure. That's my next goal, to win the big tournaments," he said.
Raonic was returning from almost a month on the sidelines due to a right leg injury and enjoyed a 6-3, 7-5 victory over Serbia's Viktor Troicki.
The Canadian was in charge of the opening set and at 3-1 up in the second, it looked all over but Troicki forced things back to level at 5-5 before Raonic got the crucial break.
Intermittent rain and high winds made it tough at times for both players but Raonic said he was glad to get back on court.
"But I've put in the work that I can, I have prepared the best I can for this tournament and while I'm not necessarily in the best position right now, fortunately it is a long tournament," he said.