Former runner-up Kevin Anderson and sixth seed Adrian Mannarino bowed out in the Memphis Open first round.
Despite sending down 21 aces, Anderson – the 2015 runner-up making his return from a hip injury – went down to Damir Dzumhur 6-7 (6-8) 7-6 (7-2) 6-4 at the ATP 250 event.
A break of serve in the opening game of the third set proved crucial for Bosnia-Herzegovina's Dzumhur, who closed out victory in two hours, 36 minutes.
The only seed in action on the hard-courts on Monday departed, as Mannarino was edged by American Donald Young 3-6 7-5 7-6 (7-4).
France's Mannarino was up a break in the second and third sets after taking the first, and also gave up a 3-1 lead in the decisive tie-break.
In a battle between wildcards, teenager Reilly Opelka overcame Jared Donaldson 6-1 7-5.
The day's only other match saw Yoshihito Nishioka claim a 6-4 6-4 win over Guillermo Garcia-Lopez.