Uniondale - Frances Tiafoe lost his first match since the Australian Open quarter-finals, falling to Jason Jung of Taiwan 6-3, 7-5 on Thursday night in the second round of the New York Open.
Tiafoe was the No 2 seed after accepting a wild card into the field and had a first-round bye.
The American has a career-high ranking of No 29 after his run in Melbourne, where he lost to Rafael Nadal.
No 4 seed John Millman of Australia was also upset, losing 7-6 (7/4), 1-6, 6-4 to Guillermo Garcia-Lopez of Spain.
Two other Americans reached the quarter-finals.
No 6 seed Sam Querrey, a finalist last year on Long Island, beat Radu Albot of Moldova of 6-3, 6-4 while Reilly Opelka advanced when Denis Istomin of Uzbekistan was forced to retire after they split a pair of tiebreakers.
Results from ATP Tour New York Open tennis tournament on Thursday (x denotes seed):
Second round
Guillermo García-López (ESP) bt John Millman (AUS x4) 7-6 (7/4), 1-6, 6-4
Reilly Opelka (USA) bt Denis Istomin (UZB) 6-7 (8/10), 7-6 (8/6), 1-0 abandon
Sam Querrey (USA x6) bt Radu Albot (MDA) 6-3, 6-4
Jason Jung (TPE) bt Frances Tiafoe (USA x2) 6-3, 7-5