Frenchman Paire slumped to a 6-4 2-6 6-2 loss to Dutchman Robin Haase in the first round of the ATP 250 event played on hard courts in North Carolina.
It marked the ninth time in 2014 that Paire, sidelined by a knee injury earlier in the year, has exited in the first round.
A year ago, the 25-year-old was in the world's top 25 but a disappointing campaign has seen him almost slip out of the leading 100 players.
Paire was unable to threaten Haase in the deciding set of their match, winning just five return points.
Haase broke twice, helped by Paire's awful first-serve percentage of 24 in the third set.
Another Frenchman, Mahut, had no such problems on his way to a 6-3 6-2 victory over Slovenian Blaz Kavcic.
Mahut broke serve five times and sent down just as many aces on his way to winning in one hour 13 minutes.
American left-hander Bradley Klahn was forced into a battle by teenager Noah Rubin before completing a 6-2 0-6 7-6 (7-5) win.
Wildcard Rubin, the Wimbledon junior champion making his debut at ATP level, served for the match at 5-4 in the third set but after being broken to love there was no way back.
Exciting and unpredictable German Dustin Brown needed just 49 minutes to beat Colombian Alejandro Gonzalez 6-3 6-2.
Brown's countryman Benjamin Becker also advanced, overcoming Spain's Pablo Carreno Busta 6-2 2-6 6-1.
One German was beaten in Jan-Lennard Struff, who went down to American Ryan Harrison 6-4 6-2.