Stapleton won song of the year and single of the year for "Starting Over" and took album of the year for his record of the same name. And he walked away with two more trophies as a producer on the single and album.
He then won male vocalist of the year for the fifth time and it appeared he would sweep the night before Combs ended the show by winning entertainer of the year.
"I don't deserve to win it," an emotional Combs said, "but I'm sure as hell glad that I did."
Stapleton came into the night the top nominee along with Eric Church, who was shut out.
Along with Stapleton and Church, Combs beat out Carrie Underwood and Miranda Lambert, who opened the ABC telecast with a medley of her hits, including "Kerosene," "Mama's Broken Heart" and "Gunpowder & Lead."
It was a night of big emotions for many winners.
The Brothers Osborne won vocal duo of the year for the fourth time. Lead singer T.J. Osborne, who came out as gay this year, appeared to be holding back tears as he accepted.
"It's been a roller coaster of a year, especially for me emotionally, and for you all to support me, it's been incredible," he said from the stage.
Jimmie Allen was openly tearful as he became the second black performer to win new artist of the year.
"I want to thank my father who's no longer with us for introducing me to country music," Allen said.
He recalled spending the last of his money to be able to see pioneering black country artist Charley Pride at the CMAs in 2016, then getting to perform with Pride on last year's show. Pride died of COVID-19 a month later.
Darius Rucker in 2009 was the first black artist to win the award.
In awards announced before the show, "half of my hometown" by Kelsea Ballerini featuring Kenny Chesney won musical event of the year and music video of the year.
In a year when the major categories are dominated by male nominees, Gabby Barrett was the night's most nominated woman with four nods, but the "American Idol" alum was shut out.
In winning album of the year, Stapleton beat nominees including Morgan Wallen, who was caught earlier this year yelling a racial slur. The CMA Board of Directors disqualified Wallen from individual awards, but he could still win for his work.
Wallen, who was not in attendance, got the biggest cheer by far of all the album nominees from the arena crowd.
