Jonathan Kaye carded an even-par 70 to finish alone in second place at 8-under-par 272 while Davis Love III came in at 7-under-par 273. Tiger Woods, who has won this event three times at Firestone Country Club, finished alongside Chris Riley in a tie for fourth at 6-under-par 274.
Clarke left little in doubt on Sunday in running away with his second WGC title. The Ulsterman, who won the 2000 Match Play Championship over Woods, never gave his competitors a chance to work themselves back into the tournament.
'Match play is different,' said Clarke, who pocketed $1,050,000 for the win. 'It's one on one. It's always been one of my goals to win a stroke play tournament in America.'
Clarke got his round going with a bang and sent his second shot to 10 feet at the par-5 second. He drained the putt for an early eagle and knocked his approach inside six feet for a birdie at the par-4 fourth.
He found trouble with a bogey at the fifth but landed his second shot within 10 feet at the par-4 ninth to set up birdie. Clarke added a birdie at the 11th to open a five-shot lead over the field and converted a long birdie putt at the 13th to move to 14-under.
'I was very calm today,' said Clarke. 'It is great to see progress in my swing, my short game, my mental side, everything.'
Clarke faltered with back-to-back bogeys from the 15th but the tournament had already been sealed. The 35-year-old rolled in a short par putt at the last to lock up his first win in over a year.
'It's fantastic to win another World Golf Championships event,' said Clarke. 'To be only the second player to win two of these behind Tiger is pretty good. Any time you follow anything Tiger has done is pretty good, so I'm delighted.'
Woods, who completed a career slam of the WGC events with a victory at the Match Play Championship earlier this year, was three shots back to start the day and provided the most pressure Clarke would experience all day.
The 27-year-old converted a 15-foot putt for a birdie at the first and picked up another birdie at the seventh.
At the par-4 eighth, Woods dropped his approach inside five feet and converted the birdie putt to make the turn at 9 under.
The top player in the game had a shaky back nine, however, and his challenge fizzled with three bogeys down the stretch.
Kaye, who earned his first PGA Tour victory this season at the Buick Classic, had a rocky start with three bogeys and two birdies.
The 33-year-old tallied two birdies and a bogey on the inward half to finish solo second.
Vijay Singh, Robert Allenby and Jim Furyk shot matching rounds of 69 to share sixth place at 5-under-par 275.
Trevor Immelman and Brad Faxon were one shot further back at 4-under-par 276.
Bernhard Langer, Dan Forsman and Steve Flesch finished in a tie for 11th at 3-under-par 277.