Ranked fourth in the U.S. men's pecking order behind world number 12 John Isner, Sam Querrey (61) and Steve Johnson (64), Sock has carried his stellar doubles form into singles in recent weeks, reaching the last four at the Newport International.
Sock's quarter-final upset of Isner at Newport shot his ranking to a career-high 69, three places above his current 72, and the highly-fancied Nebraskan will be eager to maintain his form ahead of next month's U.S. Open.
Americans Robby Ginepri and Tim Smyczek advanced, but sixth seed Istomin was too strong for Rajeev Ram, winning 6-1 6-4.
The 27-year-old Uzbek number one has yet to crack a maiden ATP title, though has come close in America, reaching the final at San Jose and New Haven in years past.
"I'd like to get that first title and I'd like to get it here," he told reporters.
The Atlanta Open is the start of the U.S. Open Series, a set of tournaments that are a prelude to the year's final grand slam starting on Aug. 25.
In other first round action, hotheaded Australian Marinko Matosevic topped Dominican Republic's Victor Estrella Burgos 6-0 6-2.
(Writing by Ian Ransom; Editing by Amlan Chakraborty)
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