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.
For the second year running, all horses and jockeys returned safely from the marathon steeplechase, however the 39 jockeys who started the race later refused to attend a stewards' inquiry into a false start.
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 at Claines in Worcester, having stopped surgery practice earlier this year. Pineau De Re was his first runner in the National.
"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 BBC Sport.
"John [Provan, the owner] is one of my oldest racing friends. We've been coming here for over 20 years, before I started training - he had horses before me and taught me a lot about it.
"Leighton is a top-class jockey - he had a plan and delivered it superbly. One of the reasons I put him on the horse was because he's had a bit of a comeback season. I just thought maybe, with his confidence high, he could go one better."
There was a 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, named after a wine and bought out of Ireland last year after he won the Ulster National, as he moved 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.
Hobbs said of Balthazar King: "He's amazing. He ran well in the race last year but finished much better this time.
"I have enormous pride in the horse - he's one of the best, most consistent, tough horses, he tries so hard."
Third-placed Double Seven, saddled by former Grand National-winning trainer Martin Brassil, was the mount of AP McCoy.
The 18-time champion jockey said: "Martin had the horse in great form, but the ground was a fraction dead for him.
"Jumping the third-last I thought I had a chance of winning, but then I think the dead ground found him out.
"Dr Newland and Leighton are nice people and it's great for them to win it."