Woods parred No. 7 - the first sudden-death hole - after he made a birdie putt at No. 18 to erase Mediate's one-stroke lead and extend the playoff.
It's Woods' 14th major championship, his third U.S. Open title and he becomes the first golfer in history to win seven tournaments on one golf course.
Mediate, 46, was bidding to become the oldest U.S. Open champion and oldest first-time major winner in golf history. He overcame a three-shot deficit through 10 holes, with birdies at No. 13, 14 and 15 - the last giving him a one-stroke lead after Woods bogeyed No. 13.
Mediate led by one after 13 and was even par through 17 holes. But Woods reached the par-5 18th green in two strokes and two-putted for birdie. Mediate had a 16-foot putt for birdie and the win on 18, but ran it three feet past the hole. He had a similar length putt on the sudden-death hole, but pushed it wide right.
Both men played the first 18 holes in even-par 71. Mediate hit a fiarway bunker with his tee shot on the final hole, then landed near the grandstand on the left side of the front of the green. He chipped to within about 16 feet, but was unable to extend the round any further.