Seventh seed Alex Bogomolov Jr suffered a shock in the opening round of the BB&T Atlanta Open when he was beaten by teenager Jack Sock.
The 19-year-old Nebraska native stunned his 29-year-old Russian opponent 6-2 4-6 6-4 to claim his third tour-level victory.
Sock's success set up a second-round meeting with another American wild card, Steve Johnson, who overcame compatriot Donald Young 6-3 3-6 6-3.
In contrast to Bogomolov, fifth seed Kevin Anderson made smooth progress in Georgia, the South African seeing off Italian Paolo Lorenzi 6-4 6-3.
Luxembourg's Gilles Muller was another straight-sets winner, ousting Australia's Marinko Matosevic 7-6 (7/5) 6-4. He will next face second seed and defending champion Mardy Fish.
The top four seeds - John Isner, Fish, Kei Nishikori and Andy Roddick - all received first-round byes.
Fourth seed Roddick's first involvement will be a second-round clash with Frenchman Nicolas Mahut, who toppled Chile's Paul Capdeville 6-3 3-6 6-4.
Also on Monday night, Russia's Igor Kunitsyn defeated American wild card Brian Baker 6-4 6-7 (3/7) 6-3.