Simon, seeded second and ranked 25th, had not reached an ATP semifinal in the United States before the Indianapolis tournament, which moved to a hard-court surface in 1988.
"That's special for me because it's not the kind of court I like to play usually,'' said the 23-year-old Simon, who earned his fourth career ATP title. "I beat some good players on this kind of court, that's why it's a very good thing to win this tournament.''
Tursunov, seeded third and ranked 32nd, was hoping to join Pete Sampras and Andy Roddick as the only players to win back-to-back singles titles in Indianapolis since 1981. Tursunov beat Frank Dancvic in last year's final.
"To be honest, I didn't really feel that pressure,'' said Tursunov, who was seeking his fifth career ATP title. "I do get a bit of jitters and my game doesn't work that well when I'm nervous. I really have to go for my shots and there's very little margin for error.''
Tursunov finished with 32 unforced errors, compared to 13 by Simon, and failed to convert any of his nine break-point chances.
"He played a few good points and then I made some silly errors,'' Tursunov said.
Simon said he didn't feel like the underdog, despite playing against the defending champion.
"Like every match I play, I think I can win,'' he said. "Even if I'm playing bad or good, I think I have a chance. ... I fight every time.
"Today was my best match of the week. I was very close to playing my best tennis.''
Tursunov was impressed with Simon's performance.
"I've never played him before, so it's a bit surprising how many balls he can get to, and he moves really well around the court,'' Tursunov said.
Ashley Fisher and Tripp Phillips won the doubles championship with a 3-6, 6-3, 10-5 victory over Scott Lipsky and David Martin. It was the first doubles title in Indianapolis for both Fisher and Phillips.
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