Roddick's defeat in two hours, three minutes, left the former world number one without a title since winning in Lyon nine months ago but he does return to the world's top 10.
Blake, who moves to a career-high fifth in the world, enjoyed his second win a row over second-seeded Roddick whom he also beat at Queen's Club in London last month.
Blake, who has already won in Sydney and Las Vegas this year, is 2-6 against Roddick after losing the first six matches to his fellow American.
"This is one of the best finals I've ever played," Blake told reporters. "I had to play like that to beat a champion like Andy.
"I played my best tennis, it's very satisfying to have done it in the final."
The winner said he hoped it marked a revival for American tennis after disappointments at the French Open and Wimbledon.
"Andy and I wanted to prove that U.S. tennis is back now," Blake said. "We're on our surface now and we want to do well going into the U.S. Open and hopefully for the rest of the year.
"I like the way that things are going."
Blake, who lost in the first round last year, improved to 37-15 for the season as he took his record in finals to 6-6.
Roddick, who dropped out of the world's top 10 for the first time in four years after Wimbledon, served 17 aces and struck 41 winners. But it was not enough to beat a determined Blake who saved 10 of a dozen break points.
"This is the only final besides the 2004 Wimbledon final (which he lost to Roger Federer) that I can say I've played my best tennis and lost," Roddick told reporters.
"Sure I'm disappointed now, but I'm sure I will look back at this week as a success. Hopefully this is a turning point."
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