Dubois dropped his compatriot to the canvas in the opening round with a stinging right, the referee delivering a standing eight count.
The 27 year-old proceeded to tear up the pre-fight predictions as swiftly as he ripped into his opponent.
Joshua, 34, took another hammering in round two but managed to ride out the storm before round three came crashing down around him again.
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With Dubois landing more fizzing right-handers, Joshua was literally on the ropes before being saved by the bell.
He could barely stand at the end of the fourth, after going down again with two minutes remaining, and then it was all over in the fifth with the painstaking rebuilding of his career suddenly in ruins.
After landing a few promising blows, any signs of a fightback faded with a right to the chin that sent Joshua down.
The former IBF, WBA and IBO champion this time unable to get back on his feet.
“l have only got a few words to say: Are you not entertained?” declared Dubois after the biggest win, and first at Wembley, of a 24-fight career with two defeats.
“Im a gladiator, I’m a warrior to the bitter end. I want to get to the top level of this game and reach my full potential.
“I’ve been on a rollercoaster ride. This is my time, this is my redemption story, and I’m not going to stop until l reach my full potential.”
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