The world number six, making his debut in Dubai, saved seven break points in the first set before taking full advantage of Paire's troublesome right knee and prevailing in 81 minutes.
"It's never easy playing Benoit. He has a great serve and a great backhand," Nishikori said.
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"I think the key was the longest game at 2-1 in the first set. I was able to get the game. I was more confident. If he broke back, anything could have happened. It was a good match."
Top seed Nishikori will next take on Polish qualifier Hubert Hurkacz who beat another Frenchman in Corentin Moutet 6-3 7-5.
The seeds continued to tumble as Daniil Medvedev and Marin Cilic crashed out in the opening round.
World number 113 Ricardas Berankis stunned eighth seed Medvedev 6-3 6-3 while Frenchman Gael Monfils knocked out third seed and former U.S. Open champion Cilic 6-3 4-6 6-0.
"I was feeling good today. I'm really happy with my game," 28-year-old Berankis said. "The plan was to stay as close as possible and not to get in his game, which is to get into those long rallies which he loves."
The Lithuanian qualifier, who won his 11th ATP Challenger title last month in Rennes, faces Denis Kudla next after the American rallied past Matteo Berrettini 2-6 7-5 7-5.
Twice finalist Tomas Berdych faced a stern test from lucky loser Ilya Ivashka before prevailing 6-4 4-6 7-6(4) in two hours and 30 minutes.
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