The only two seeded players in action Monday lost their first-round matches in the Delray Beach (Fla.) Open.
Japan's Yoshihito Nishioka upset fifth-seeded Australian John Millman 3-6, 6-4, 6-2, and South Korea's Soonwoo Kwon got past seventh-seeded Frenchman Adrian Mannarino 1-6, 6-3, 6-2.
Nishioka, a 24-year-old who is ranked 63rd in the world, won the match in just under two hours.
Kwon, a 22-year-old who is rated 82nd, took advantage of shaky serving from Mannarino, who put just 48 percent of his first serves in play.
The day's other four matches were all won by U.S. players: Frances Tiafoe, Mackenzie McDonald and wild-card entrants Ryan Harrison and Brandon Nakashima.
Third-seeded Cristian Garin of Chile saved four match points to get into a third-set tiebreak, then pulled out a 4-6, 7-5, 7-6 (5) win over Slovakia's Andrej Martin in the first round at Rio de Janeiro.
Martin led 6-5, 40-0 on Garin's serve in the last set, but Garin saved those three match points and one more before winning the game. Garin jumped ahead 6-2 in the tiebreaker to set up four match points, and he finally put away the match on the last of those four.
In other opening-round action, Pablo Andujar defeated Fernando Verdasco 6-3, 6-3 in an all-Spanish battle. Argentina's Federico Coria and Federico Delbonis, Spain's Pedro Martinez and Brazil's Thiago Seyboth Wild also moved into the second round.
Open 13 Provence
Sixth-seeded Benoit Paire topped wild-card entrant Gregoire Barrere 6-4, 7-6 (1) in a showdown of French players during the opening round at Marseilles, France.
Paire had a 13-4 edge in aces. He won 91 percent of his first serve points to 81 percent for Barrere, who never broke serve.
The other first-round winners were Kazakhstan's Alexander Bublik, who eliminated Hungary's Marton Fucsovics 6-4, 7-5, and Sweden's Mikael Ymer, who edged France's Richard Gasquet 6-3, 3-6, 7-5.
--Field Level Media