Nishikori has shaken up his longtime schedule this season and is playing Dubai for the first time for a welcome change of ATP scenery after limiting himself in the past to North American venues including the defunct Memphis event and Delray Beach.
Victory over the unpredictable Paire who is prone to throwing and smashing racquets in moments of despair, lasted for 81 minutes.
"It's never easy playing Benoit, of course. Great serve, great backhand. Tricky player. Good dropshot, good touch," was Nishikori's analysis.
Lithuanian qualifier Ricardas Berankis knocked out another seed after Monday exits of Karen Khachanov and Milos Raonic as he beat Russian number eight Daniil Medvedev 6-3, 6-3.
American Denis Kudla eliminated last season's Gstaad winner Matteo Berrettini of Italy 2-6, 7-5, 7-5 and Egor Gerasimov of Belarus beat Dutchman Robin Haase 7-6 (7/2), 7-6 (7/5).