Andy Ruiz punches Anthony Joshua during a heavyweight championship boxing match on Saturday in New York. Photo: AFP

Anthony Joshua's bid to make a splash in his US debut ended in misery for the three-belt heavyweight world champion with a stunning loss to underdog Andy Ruiz at Madison Square Garden on Saturday.

Ruiz recorded a monster upset, by knocking down Britain's Joshua four times to take the World Boxing Association, International Boxing Federation and World Boxing Organization titles.

The 29-year-old Ruiz came into the fight as a massive 32-1 underdog. But he won it by TKO in the middle of the seventh when the referee stopped it at 1:26 of the round after the fourth knockdown.

Ruiz, sent to the canvas once himself, knocked Joshua down twice in the third round and twice more in the seventh.

Joshua (22-1, 21 KOs) had a massive height and reach advantage as he weighed in at a chiselled 247 pounds (112.4 kilos) compared to the portly Ruiz, who beefed up to 268 pounds compared to 250 for his most recent fight. 

Ruiz, who has won four fights in a row, looked fearless and poised while Joshua - who delivered 21 knockouts in his 22 victories - ­never seemed to recover from the first knockdown early in the third round.

Ruiz (33-1, 22 KOs) has been underestimated because of his physique, but he knew what was at stake and how fortunate he was to get a second chance at a world title.

He was a late replacement for Jarrell Miller, who withdrew from the bout with Joshua after failing three drug tests in April.

Joshua was knocked down for the first time in the third when Ruiz hit him with a left hook to the temple. Realizing he had the champ in trouble, Ruiz then charged forward and got the second knockdown by connecting on a straight right. 

Joshua got up at the count of eight but it was late in the round and he was saved by the bell.

Ruiz was the first to go to the mat when he got hit by a left hook from Joshua earlier in the third.

Joshua got up after the third and fourth knockdowns in the seventh but he spit out his mouthguard and the referee waived it off after the fourth trip to the canvas while he leaned on the ropes.

Joshua, who won a gold medal at the 2012 Olympics, was coming off a nine-month layoff since knocking out Alexander Povetkin in September.

Ruiz's ambush win is being hailed by some as one of the ­major upsets in heavyweight history, ranking with 42-1 underdog Buster Douglas knocking out Mike Tyson in 1990 and Leon Spinks' 15-round split decision over Muhammad Ali in 1978.