Bernard Tomic made a shock first-round exit in Memphis as Fabio Fognini was beaten in Buenos Aires on Tuesday.
Australian fifth seed Tomic was stunningly beaten by Darian King 6-4 6-4 at the Memphis Open.
Qualifier King became the first player from Barbados to win an ATP World Tour main-draw match in the Open Era, while Tomic now holds a 2-3 record this year.
Also in Memphis, last year's runner-up Taylor Fritz battled past eighth seed Lu Yen-hsun 4-6 7-6 (7-4) 7-6 (9-7).
American teenager Fritz saved three match points and came from 6-4 down in the third-set tie-break.
Steve Darcis, the 2008 champion, was the only seed to advance, the Belgian overcoming Radu Albot 7-5 3-6 6-4.
Ryan Harrison beat Konstantin Kravchuk 6-3 7-5, qualifier Matthew Ebden claimed a 6-7 (4-7) 6-3 6-1 win over Peter Polansky and Tim Smyczek recorded a 6-3 5-7 6-3 win against Frances Tiafoe in an all-American affair.
At the Argentina Open, Italian seventh seed Fognini - the 2014 runner-up - went down to one-time champion Tommy Robredo 6-4 6-3.
The only other two seeds in action on the clay in Buenos Aires, Albert Ramos-Vinolas and Joao Sousa, came through their openers.
Sousa was too good for local Horacio Zeballos 6-2 7-6 (7-4) and Ramos-Vinolas battled past Guido Pella 6-7 (8-10) 6-4 7-6 (8-6).
Alexandr Dolgopolov brought an early end to Janko Tipsarevic's tournament with a 6-3 6-3 victory.
There were also wins for Diego Schwartzman, Carlos Berlocq, Alessandro Giannessi and Guido Andreozzi.