Fahrenheit 9/11, an emotion-charged documentary that tears into Bush in the run-up to November's presidential election, won the Palme d'Or on Saturday.
"I have this great hope that things are going to change," the Oscar-winning director, overwhelmed by the standing ovation, said.
"I want to make sure if I do nothing else for this year that those who have died in Iraq have not died in vain."
Moore was the big winner on a night otherwise dominated by Asian films which took three top prizes to show they are now a major force in world cinema.
Moore's diatribe focuses on how America and the White House reacted to the 11 September 2001 hijacking attacks and traces links between the Bush family and prominent Saudis including the family of Usama bin Ladin.
It then switches to the war in Iraq with graphic footage of Iraqi wounded and prisoners being abused by American troops.
Fahrenheit 9/11 had already whipped up an international media storm after Walt Disney barred its Miramax film unit from releasing such a politically polarising work in a US election year.
"I have this great hope that things are going to change. I want to make sure if I do nothing else for this year that those who have died in Iraq have not died in vain"
Miramax is negotiating to buy back distribution rights from Disney in the hope of releasing the film in the US in July.
Two years ago, the director's anti-gun lobby documentary Bowling for Columbine won a special prize at Cannes and went on to gross $120 million worldwide and win him an Oscar.
Thanking the jury headed by cult director Quentin Tarantino, Moore said: "You will ensure that the American people will see this movie."
Moore's win capped a politically charged festival with documentaries and films reflecting troubled times and French showbusiness workers staging demonstrations and sit-ins to protest against cuts in their welfare benefits.
Tarantino, who screened his Kill Bill revenge saga out of competition, also rewarded Asian films reflecting his passion for martial arts movies.
However, the best actor award was a surprise, going to 14-year-old Japanese actor Yagura Yuuyi for his captivating performance in Nobody Knows, about four children abandoned by their mother in Tokyo to fend for themselves.
Yagura missed the awards ceremony because he had to return to Japan to sit school exams.
Tarantino rewarded Asian films
in this year's ceremony
The best actress award went to China's Maggie Cheung for her role as a woman trying to kick a drug habit and win back her son in Clean, by French director Olivier Assayas.
The Grand Prix went to ultra-violent Korean film Old Boy, the story of a man imprisoned for 15 years who must find out who captured him and why.
France also enjoyed two awards. Agnes Jaoui and Jean-Pierre Bacri won the best screenplay award for Jaoui's film Comme une Image, the tale of a 20-year-old desperate for love and attention from her callous father.
And Tony Gatlif was named best director for Exils, about a man going back to Algeria from France to find his roots.