Youzhny's triumph extended the Russian men's winning streak at the annual indoor tournament, which was celebrating its 20th anniversary this year, to six consecutive years.
After losing a tight first set in the tiebreak 7-5, Youzhny reeled off eight consecutive games to even the match and take a 2-0 lead in the decider.
Tipsarevic, playing in his first Tour final, saved four match points in the ninth game, but the world number 30 sealed his first Moscow crown and his first title since January 2008 at his next opportunity in the following game.
"Playing at home, in front of my family and friends, definitely put extra pressure on me but it made my victory taste even sweeter," the 27-year-old Muscovite told a news conference.
"Finally, after 11 attempts I was able to win in Moscow. I got a lucky draw this time but I had to work hard to earn it."
RIB INJURY
Tipsarevic, who beat Youzhny in both their previous matches, was gracious in defeat.
"I didn't lose today, Misha beat me. He was the better player," said the 46th-ranked Serb, who also played a three-set doubles match late on Saturday.
"Definitely playing on Saturday night took its toll. I was physically down after the first set."
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