Referee Howard Foster finally stepped in at the start of the 11th round to signal the end of the fight with Wardley bleeding heavily from the bridge of the nose and with his right eye almost closed.
Dubois rose twice from the canvas, including being dropped by a right hook in the first 10 seconds of the fight, to pulverise Wardley and become a world heavyweight champion for the second time in his career.
"It was a war. We came through the sticky moments. Thank you Fabio for that," said Dubois, who was previously IBF champion after the belt was vacated by Oleksandr Usyk in 2024, with the Ukrainian winning it back in July 2025.
"What a great fight. What a great battle, man".
The win was Dubois's 23rd as a professional in 26 fights while Wardley now has a 20-1-1 record.
Veteran promoter Frank Warren, who manages both men, said it was the best heavyweight fight he had ever put on and confirmed there was a rematch clause in the contract.
For some viewers, however, it was also an uncomfortable watch that could have been stopped earlier.
The 31-year-old Wardley, who was promoted to WBO champion last November after Usyk vacated the title, was making his first defence and showed immense heart as he took a tremendous beating yet refused to capitulate.
He had his opponent on the floor, a blow Dubois, 28, later dismissed as a 'flash knockdown', almost with the opening bell still sounding.
Dubois was back on one knee in round three but came close to a stoppage in the sixth with the reigning champion bleeding heavily and on the ropes.
The Londoner continued to land blow after blow on Wardley, who wobbled but refused to give up.
His corner inspected the facial wounds after the eighth and doctors and the referee took a look in rounds nine and 10 but still the fight continued, with Wardley increasingly struggling to stay on his feet and fighting on instinct.
"You witnessed something special tonight," Warren told the BBC. "Two men baring their hearts and souls in the ring, gave everything, didn't leave one bit outside the ring.
"They were getting hit with bombs that would take people out and they stood it."