The duo accepted the song of the year award for the gospel-tinged "Believe," written by Craig Wiseman, who also co-wrote the 2005 song of the year, "Live Like You Were Dying."
Newcomer Carrie Underwood, last year's "American Idol" winner, was nominated in four categories, the most for any woman. She claimed awards for top new female vocalist and single of the year for "Jesus Take the Wheel," a song she performed on the show.
"I wouldn't be here if God hadn't opened all the doors for me," she told the audience.
Brad Paisley, who led the list of nominees with six, got the award he said he wanted, winning album of the year for "Time Well Wasted." Jason Aldean, whose song "Why" is No. 1 this week, was named top new male vocalist.
Brooks & Dunn and Sugarland had five nominations each and Rascal Flatts had four, tying Underwood. Along with her Sugarland nominations, lead singer Jennifer Nettles also was up for her crossover hit with Bon Jovi, "Who Says You Can't Go Home."
Sugarland took away honors for top new duo or vocal group.
Keith Urban was top male vocalist for a second year.
Trace Adkins, dressed all in black — from his cowboy hat to his leather suit — added a Las Vegas touch to the program as he performed "Honky Tonk Badonkadonk" while surrounded by shimmying showgirls.
His performance was preceded by a more traditional country salute to the nation's soldiers that brought many in the audience to their feet. Gretchen Wilson also paid tribute to the soldiers, the Bible, working men and other country traditions in the song "Politically Incorrect."
This year's 41st annual ceremony, at the MGM Grand, was the third to be held in Las Vegas after it moved from Los Angeles. Airing on CBS, it went up against part one of the two-part "American Idol" finale on Fox.
The (Nashville) Tennessean reported Tuesday that the academy wants to move the awards show to April to escape the conflict with "Idol," TV's top-rated show. The size of the "Idol" audience has dwarfed that for the awards show the past three years.
Reba McEntire hosted this year's show for the eighth time. Besides Paisley, Brooks & Dunn, Underwood, Urban and Rascal Flatts, other performers included award nominees Miranda Lambert, Toby Keith, Dierks Bentley, Montgomery Gentry, Big & Rich, Martina McBride, Gretchen Wilson and Kenny Chesney.
A late addition to the show was a planned tribute to the late Buck Owens, who died in March, with Dwight Yoakam performing his version of Owens' trademark Bakersfield Sound along with Paisley, ZZ Top's Billy Gibbons, and Owens' son, Buddy.
Vince Gill received the Home Depot Humanitarian Award for his community service and charitable giving of his time and talent — a trophy and a playground built in a city of his choice. He said on Tuesday that probably would be New Orleans. Previous winners include McEntire, McBride, Lonestar and Neal McCoy.
Awards announced before the broadcast included: producer, Buddy Cannon; on-air personality (national), Blair Garner; on-air personality (major market), Gerry House; on-air personality (medium market) Scott Innes; on-air personality (small market), Becky Austin and Brad Austin; radio station (major market), WFMS-FM; radio station (medium market), WUSY-FM; radio station (small market), (tie) WGSQ-FM, WYCT-FM; bass player, Michael Rhodes; fiddle player, Jonathan Yudkin; guitar player, Pat Buchanan; percussionist-drum, Shannon Forrest; piano-keyboard, Mike Rojas; specialty instrument, Bryan Sutton; steel guitar, Paul Franklin.
The 3,000 members of the academy select the nominees and winners of the awards.
List of winners: