Anthony Joshua 'Drake Curse' Strikes Again!!! Champ Loses by TKO to Andy Ruiz Jr.

Anthony Joshua's gotta be kicking himself Sunday morning after losing in one of the biggest upsets in boxing history -- and he's got no one to blame but himself ... and possibly Drake.

AJ lost his 3 heavyweight titles in Madison Square Garden Saturday night to Andy Ruiz Jr. -- who was an 11-1 underdog -- by TKO in the 7th round. It's being called the biggest upset since Mike Tyson lost to Buster Douglas in 1990 ... but we all should've seen it coming when Joshua cozied up to Drake.

Back in March, the then WBO, IBF and IBO heavyweight champ posted a pic with Drizzy, and even went so far as to say he was going to “break the curse” on June 1. Oops.

Daaamn, did Andy Ruiz really just expose Anthony Joshua at MADISON SQUARE GARDEN 💀😳

Love an underdog story 🙌 pic.twitter.com/QTK6u9Ugcm

Drake's got a pretty extensive track record of jinxing teams -- just ask Alabama football, Italy's Roma soccer team, Conor McGregor and Serena Williams.

He's even mocked the curse lately -- wearing Philadelphia 76ers shorts to jinx that team last month when they were playing his beloved Toronto Raptors ... and it worked.

Anyway, congrats to Andy Ruiz Jr. ... who'll probably fight a rematch against Joshua. We know who WON'T be walking either fighter into the ring.

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