Gretchen Wilson won for both female vocalist and best new artist despite a sometimes in-your-face approach to the Nashville establishment.
Australian Keith Urban took male vocalist and album awards and Kenny Chesney was named entertainer of the year, just eight days after his surprise marriage to actress Renee Zellweger, who was on a movie set and missed Tuesday night's show.
Two poignant songs paid off for Tim McGraw and for Brad Paisley and Alison Krauss, who took home two trophies each.
Chesney laughed off questions about his marriage after the show, saying only that he would spend his evening going to a party and doing a little gambling.
"This is very special, no doubt about that. The magnitude of it is going to hit me about 2 o'clock in the morning after a couple of drinks," he said. "I won my first award at the academy and it's always a real special place."
Urban and Wilson were stunned by their awards.
"I'm just blown away that we've come to this point," Urban said from Belfast, Northern Ireland, where he was touring. "If there's just one award that I could have picked to win, it's album of the year."
Wilson, who flaunted a no-nonsense attitude in her breakout hit "Redneck Woman," cried as she accepted the female vocalist of the year trophy, ending a three-year run for Martina McBride.
"I don't even really know what to say, except for thank you," Wilson said. Backstage, she choked up again, saying, "It's been an amazing year for me."
McGraw — nominated in a leading six categories — took top single and song honors for his hit "Live Like You Were Dying," which has special meaning for him because his father, former pro baseball pitcher Tug McGraw, died of cancer last year.
The awards show had an international flavor. Along with Urban in Belfast, camouflage-clad Toby Keith performed "As Good as I Once Was" for a crowd of clapping U.S. troops in Iraq, saying "Welcome to honky-tonk university, ya'll. We're in Baghdad."
Paisley and Krauss took video and vocal event honors for their haunting duet "Whiskey Lullaby." Paisley said he had initially been concerned that radio wouldn't play the song because of its dark themes.
"It's death and drinking. It's summertime for God's sake," he said.
Veterans Brooks & Dunn beat out several newcomers for top vocal duo, their record 19th career award.
"This far down the road, it really feels good ... they call your name out time after time," Ronnie Dunn said.
Another veteran, Faith Hill, ended a five-year absence from the awards show with a performance of "Mississippi Girl." Wearing a sheer green blouse and jeans, Hill looked rejuvenated as she pumped her fist and strutted across the stage.
Retired superstar Garth Brooks was greeted by more than 20 seconds of applause as he walked onstage to honor his friend Chris LeDoux, who died March 9 of liver cancer.
"I'm not saying you're saying this but, I've missed you too," Brooks told the crowd, doffing his cowboy hat.
The Humanitarian Award went to Neal McCoy, who said he was "tickled to death."
Trophies were presented in 12 categories over three hours, allowing the performance-driven CBS telecast from the Mandalay Bay Resort to focus as much on entertainment as awards.
The honors were determined by the 3,000 members of the California-based academy, except for the humanitarian and video awards, which were decided by fans.