Vijay Singh finished alone in third at 21-under-par 267 after a round of 65. He was followed by Jerry Kelly and David Toms, who were tied at 20-under-par 268.
Woods dominated each day at Mount Juliet Estate and the final round was no different. Woods was always in control en route to his second victory at the American Express Championship, despite late heroics by Goosen, who eagled the par-5 17th to pull within one of the lead, and a bogey at the closing hole, Woods' only dropped shot of the tournament.
'It means a lot when you play against the best and come out on top,' said Woods, who earned his 34th career win on the PGA Tour. 'Forty-nine of the top 50 players of the world are here this week. A lot of guys did play well and it was nice to keep it up.'
Woods had a five-stroke advantage after Round 3 and continued the blistering pace with a birdie at the opening hole after he knocked his approach to 14 feet.
At the fourth, Woods landed his second shot inside 15 feet for birdie and two-putted for birdie at the par-5 fifth to reach 22-under.
While several of his competitors put together solid rounds, Woods again distanced himself from the field after he lifted his second shot over a tree to 14 feet at the par-5 10th. He drained the putt for eagle and a four-shot lead.
Woods continued to roll with a six-foot birdie at the par-3 14th, but Goosen suddenly made things interesting on his way to a record round.
Goosen was part of a six-way tie for second to start the day and picked up four birdies on the front nine to make the turn at minus-18. He birdied the 10th to pull within three, but faltered with a bogey at the very next hole.
The 33-year-old responded well with back-to-back birdies from the 12th and added a pair of birdies starting at the 15th before the eagle at the par-5 17th moved him within one of Woods.
Goosen parred the 18th for a round of 62 to match the course record, set earlier in the round by Sergio Garcia.
'Today was one of the best rounds I've ever played,' said Goosen. 'I've shot 62 a couple of times at Loch Lomond, but this tops that. Overall, I'm very happy with the week.'
Woods seemed to buckle under the pressure with an errant drive at the par-5 17th and a second shot that found the rough, but the 26-year-old was never in doubt. He knocked his third shot to 18 feet and ran home the putt for fist-pumping birdie and a two-shot lead.
'That was probably one of the best shots I've hit all week,' said Woods of his whack from the rough. 'I knew that was probably going to be the shot of the tournament.'
Woods, whose last bogey came at the WGC-NEC Invitational in August, had four feet to complete a flawless tournament, but he sent the ball right of the hole. Even with the late bogey, Woods walked away with his sixth title in 12 World Golf Championships starts and a first-place prize of $1 million.
Scott McCarron, Woods' playing partner on Sunday, finished six shots back at 19-under-par 269 after a round of 67. He was followed by Garcia, who was phenomenal on his way to a course record.
The young Spaniard didn't pick up his first birdie until the fifth, but a stretch of four straight birdies around the turn started him on his way.
Garcia added a birdies at 12, 14 and 16 before a long eagle try at the par-5 17th found the center of the cup en route to a round of 10-under 62.
'I'm happy I played very solid today, very consistent,' said Garcia.
Davis Love III finished alone in eighth at 17-under-par 271, while Michael Campbell and Bob Estes were one back at 16-under-par 272.
Final scores from the WGC-American Express Championship