The sentimental favorite won album of the year, record of the year and best pop collaboration for his ballad with Norah Jones, "Here We Go Again," as well as best pop album.
"I'm going to cry, actually," Jones said as she accepted the trophy for record of the year. "I think it just shows how wonderful music can be. It's at a hundred percent with Ray Charles."
Alicia Keys and actor Jamie Foxx performed a piano duet on "If I Ain't Got You/Georgia on My Mind" in a special tribute to Charles during the broadcast. Foxx is nominated for an Academy Award for his portrayal of Charles in the 2004 biopic "Ray."
included Keys and Usher, each nominated for eight Grammys. By mid-evening Keys had won four while Usher had three. They shared one award, for best R&B performance by a duo or group with vocals for their No. 1 duet, "My Boo."
U2 also had three awards, including best rock performance by a duo or group, while Green Day, the most nominated rock act with six nods for their politically charged punk rock opera "American Idiot," won best rock album.
"Rock 'n' roll can be dangerous and fun at the same time, so thanks a lot," lead singer Billie Joe Armstrong said as he accepted the award.
Keys was chasing a record Grammy haul - she could have won more than any other woman in one evening. In 2002 Keys won five Grammys for her debut album, "Songs in A Minor," becoming only the second woman to win that many in one night. (Lauryn Hill won five in 1999; so did Jones in 2003.)
The most nominated artist of the year may be the most multifaceted - Kanye West, the songwriter-producer who made his rap debut in 2004 with the cutting-edge CD "The College Dropout." West was nominated for 10 Grammys, including album of the year. In the pre-telecast ceremony he won two, including best rap song for "Jesus Walks."
But he was upset in the best new artist category, losing to Maroon 5 in a race that also included country singer Gretchen Wilson, the Los Lonely Boys and soul siren Joss Stone.
Maroon 5's Adam Levine seemed almost apologetic after winning.
"Kanye West, I want to thank you so much for being wonderful," he said. Soon afterward, the camera cut away to West, who looked less than pleased.
Some expected West to have a meltdown like at the American Music Awards, where he complained bitterly backstage after losing the same award to Wilson. But he went on to deliver an eye-popping performance of "Jesus Walks" and an emotional acceptance speech for the best rap album award.
After referencing the car accident a few years ago that almost took his life, West promised to live life to the fullest: "I plan to celebrate and scream and pop champagne every chance I get because I'M AT THE GRAMMYS BABY!"
He also referenced his American Music Awards embarrassment. "Everybody wanted to know what would I do if I didn't win. I guess we'll never know," he said, holding his trophy up high.
At least West didn't have to wait decades to get a trophy, as did some veterans finally honored by the Recording Academy.
Steve Earle's left-leaning "The Revolution Starts ... Now" won for contemporary folk album.
Rod Stewart - who was beaten out by Tony Bennett in both 2004 and 2003 - finally won what is the first Grammy of his career. The 60-year-old rocker was honored in the traditional pop vocal album category for his recording of romantic golden oldies, "Stardust ... The Great American Songbook Vol. III." Stewart, who has been passed over 13 times before, missed the big moment Sunday - instead of being at the Grammys, he was on tour in Australia.
Another no-show at the ceremonies: former president Bill Clinton, who won in the spoken word category for the recorded version of his autobiography, "My Life." It's a second win for Mr. Clinton, who won last year for a recording aimed at children, and the third win for the Clinton family. Sen. Hillary Clinton won in 1997 for her book, "It Takes A Village."
Brian Wilson, who released his album "Smile" after a more than three-decade wait, won best rock instrumental performance for "Mrs. O'Leary's Cow." He had never been honored before, even as leader of The Beach Boys. The big irony: the man who did more for vocal harmony than anyone in rock 'n' roll won in an instrumental category.
"I waited 42 years for this Grammy and it was well worth the wait," Wilson said backstage. "It represents triumph and achievement in music that I feel that I deserved, and I'm really glad I won."
The oft-maligned Britney Spears also won her first Grammy - best dance recording for "Toxic."
Spears wasn't present, but another newlywed was on hand: Jennifer Lopez performed a duet in Spanish with new husband Marc Anthony, their first public performance together.
Other performers included Green Day, whose rollicking performance was bleeped by the censors; and U2.
Perhaps the evening's most exhilarating performance was from Melissa Etheridge. The rocker, who is battling breast cancer, took to the stage for a tribute to Janis Joplin with a shaved head but strong voice, and received a standing ovation for her stirring performance with Stone.