The defending champion dropped only two points on first serve to wear down Sock, who became increasingly frustrated as the match progressed in searing heat, at one stage arguing with the umpire after a line call was reversed on replay.
"It was not easy conditions at all in the heat today," Isner said. "I thought I played pretty well. Jack is a really good player. I wanted to win that match."
The world number 12 clearly feels at home in the state where he went to college at the University of Georgia.
But the first set almost slipped away when Sock had a break point at 5-5, only to hit the tape with a backhand down the line.
Buoyed by the reprieve, Isner finally broke serve to take the set in the next game, a 14-minute marathon as Wimbledon doubles champion Sock staved off two set points.
The first nine games of the second set went with serve before Sock frittered away a 30-0 lead in the 10th game.
He saved two match points, before double-faulting on the third to hand Isner victory.
The towering North Carolina native has won eight ATP titles, his most recent in Auckland in January.
He has a 2-0 career head-to-head record against world number 94 Sela, who beat German Benjamin Becker 6-3 3-6 6-3 in the night semi-final.
The Israeli has qualified for only his second ATP final, six years after his first in Beijing, and will bid for his maiden title at the age of 29.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Ian Ransom)
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