Pineau De Re, ridden by Leighton Aspell and trained by Dr Richard Newland, won the 167th Grand National at Aintree at odds of 25-1.
The 11-year-old beat Balthazar King (14-1) by five lengths, with Double Seven (10-1 joint favourite) third, Alvarado (33-1) fourth and Rocky Creek (16-1) fifth.
Teaforthree, the 10-1 joint favourite, fell as 18 of the 40 horses finished.
Aspell, 37, had finished second on Supreme Glory in the 2003 National.
There were no horse fatalities in the race.
Pineau De Re, who finished third in the Pertemps Final over hurdles at the Cheltenham Festival in March, jumped the final fence in a clear lead and his rivals never looked like bridging the gap as he galloped all the way to the line.
Aspell, who retired from the saddle in 2007 but was tempted back two years later, said: "It's a wonderful day - this is what we do it for.
"I've been watching the National since I was a very young boy.
"As much as you enjoy sharing everyone's success, you crave a bit too.
"To get a chance to ride in the National is a great thing, and to get on one with a chance is even better."
Dr Newland trains a small stable of horses in central England, having stopped surgery practice earlier this year.
"We are so lucky to have such a lovely horse. It's a dream come true - a dream that we've had for about 30 years," he told the BBC.
There was one false start because of Battle Group's reluctance to join the other runners and when they started at the second attempt, the Johnny Farrelly-trained nine-year-old again stood motionless and took no part.
Among those to fall early in the race was former Cheltenham Gold Cup victor and dual King George VI Chase winner Long Run.
Across The Bay led for a long way until almost being taken out by a loose horse as the field headed out for the second circuit, effectively ending his chances of victory.
Aspell took his time aboard Pineau De Re, moving comfortably into contention before making his challenge.
The Philip Hobbs-trained Balthazar King, winner of the cross-country chase at the Cheltenham Festival, was never too far off the pace, as Richard Johnson rode him into the runner-up spot.
Third-placed Double Seven, saddled by former Grand National-winning trainer Martin Brassil, was the mount of AP McCoy.