Fredrik Andersson Hed of Sweden (67) and Luke Donald of England (71) tied for second at 5-under 279, one shot back of Khan. Donald was tied with Khan with two holes to play, but double-bogeyed No. 17 after hitting his drive into the trees.
The 471st-ranked Khan was asked to play in the European Tour event less than 72 hours before it started.
England's Chris Wood had led by two shots at the start of the day, but dropped six shots in his first 16 holes. Sweden's Robert Karlsson, who shot a course record 62 on Saturday, had three bogeys and a double bogey in his first 15 holes.
Khan's second victory in nine years earned him $938,000 and a playing exemption in Europe through 2015. Last November, Khan wept at the end of the Hong Kong Open after losing his Tour playing card, which he won back in qualifying school.
"I was devastated in Hong Kong last year and to bounce back like this has been fantastic," said Khan, whose other win was at the 2004 Wales Open.
Khan's connections with Wentworth run deep. As a boy, he watched Seve Ballesteros beat Ben Crenshaw in match play and later he finished runner-up in a tournament here behind countryman David Howell.
"This place is the reason I started golf," Khan said. "This place inspires me and this event is everything. Just to be here was unbelievable and I wanted to put my mark on every shot.
"I have always felt comfortable around this course — you can see your shots so clearly. Just being here is special. I didn't know I was in the tournament until Monday and to win here is so special for me."
Just as Karlsson had swept through the field in Saturday's third round with his 62, Khan and Andersson Hed followed a similar pattern in the finale after beginning seven shots behind Woods.
Khan made three birdies in his opening six holes. Adersson Hed, the recent winner of the Italian Open, opened with four in five.
Twelve players ahead of them faltered.
Danny Willett of England started out in second place at 5 under but dropped out of contention with three bogeys and a double bogey over the first nine holes on his way to a 74. Woods double-bogeyed the third hole before dropping four more shots in a 77.
As Khan was sitting on the clubhouse lead, Donald posed the main threat before his double bogey. The only consolation for Donald was the successful sinking of 3-foot birdie putt on the final green for a share of second place.
