Lady A won vocal group of the year and single of the year for the hit song about late-night hookups, while Miranda Lambert's "House That Built Me" was also an early winner, helping her kick off her 27th birthday in style.
"Thank you to my brother, Josh Kelley, for making me to move to Nashville six years ago, I love you," Lady A vocalist Charles Kelley said after his band took single of the year.
Charles Kelley made the journey with his good buddy Dave Haywood and the two met Hillary Scott a short time later. The rest has been nonstop success with their second album, "Need You Now," selling more than 3 million copies this year.
Lambert's "The House That Built Me" won video of the year and song of the year for songwriters Tom Douglas and Allan Shamblin. The tale of a family's hard-luck times mirrors Lambert's own upbringing and has resonated with fans and spurred her to nine nominations.
The Zac Brown Band won new artist of the year.
Hosts Brad Paisley and Carrie Underwood joined Keith Urban to kick off the show with "Songs Like This" before the hosts returned to poke lighthearted fun at the stars and current events.
"Nashville had a flood and it barely made news," they sang, "while up through the gulf came a bubbling crude."
They also made fun at Tiger Woods and Brett Favre, singing, "She caught Tiger with some tail it's plain to see, and Brett Favre has taken up photography."
Paisley could finally win the CMA's coveted entertainer of the year trophy Wednesday night - but he'll have to best another veteran and three relative upstart acts to make it happen. Paisley has been nominated for the award every year since 2005. Though he's won 13 CMAs since first being nominated in 2000, he's never won the biggest award.
But he faces tough competition from former winner Keith Urban, Lambert, Lady Antebellum and Zac Brown Band, the first act nominated for both entertainer of the year and new artist since Ricky Skaggs in 1982.
Lambert will be partying hard with fiance Blake Shelton, who also got off to a fast start with a win in the musical event category for "Hillbilly Bone" with Trace Adkins.
"That's how I like to start the night," Shelton said. "Now I can get drunk and relax."
The entertainer of the year category underwent something of a makeover this year as the CMA membership installed a new wave of performers in key categories, acknowledging a crossover trend that is bringing country music to more new ears than ever.
The list of omissions in that category is long and includes Underwood, last year's winner Taylor Swift and several highly successful acts long considered contenders.
Still, there's no questioning the impact Lady A, Zac Brown Band and Lambert had on the industry over the past year.
"I got to make country music history, which is what everybody hope's for when they're in this industry, because I had the most nominations out of any female ever, so ... I'm having a great day already," she said, wearing a pink gown by Sherri Hill as she walked the black carpet. "It's my 27th birthday, so I'm hoping the best birthday would to take home obviously a CMA."
Lambert rode the popularity of her acclaimed platinum album "Revolution" to a record for the most nominations for a woman in the 44-year history of the CMAs and the second most overall. Both of her No. 1 hits, the sassy "White Liar" and "The House That Built Me," were nominated in two categories, song and single of the year.
Lambert and BFF Scott of Lady Antebellum, up for five awards, were nominated together in several categories. The one that likely means the most to both is album of the year.
Lambert won that trophy at The Academy of Country Music Awards in April and it means a lot to her. At the time, Lady A was cheering her on over their own entry, the trio's self-titled debut. They released "Need You Now" in January, though, and it's sold about 3 million copies so far this year. It has produced three No. 1 hits, and they're proud of it.
Cheering for Lambert this time? Not so much.
"We definitely want to win it but if we can't we're definitely not going to be upset if Miranda runs away with it," said Charles Kelley. "I mean Dave (Haywood) and I even have a song that we wrote with Miranda and Blake on that record ("Love Song"). We would still feel some kind of pride in that."
The show was shown on ABC.