Strait, who is retiring from the road, nabbed his third trophy in the category but hadn't won the prestigious award since 1990.
He capped a night where there was no clear favorite. Shelton, Swift, Keith Urban, Tim McGraw and Florida Georgia Line won two awards each.
But Shelton won the other big award of the night - album of the year for "Based on a True Story" - besides grabbing male vocalist of the year, his fourth time winning the latter award.
Lambert, his wife, also won her fourth straight female vocalist of the year award.
"I really didn't think this was going to happen this year," Lambert said before thanking each of the other nominees.
The husband and wife have been favorites of the CMA's 6,000 voters for the last three years and Wednesday as no different.
"I had mentioned earlier today that if there was an award that would mean the most to me tonight, it would be album of the year," said Shelton, who won entertainer of the year last year and was in contention for it again this year.
Florida Georgia Line's Tyler Hubbard and Brian Kelley scored single and vocal duo of the year. Their quick tally was more proof the so-called bro country movement is the sound of the moment in mainstream country. FGL kicked off the show performing a fist-pumping medley with Luke Bryan, and very quickly returned to the stage to take the trophy for single of the year for their "Cruise" remix featuring Nelly. They also played the new song "Round Here."
"It's been a constant thing all year - we've been trying to wrap our minds around what's going on," Hubbard said backstage. "It's been a dream come true for us and a huge blessing for us and something we could have never imagined."
Kacey Musgraves - who, along with Taylor Swift, led all nominees with six - won the new artist trophy, besting a field that included Florida Georgia Line. With smart songwriting, a progressive bent and a strong sense of self like country's other top women, Musgraves made an auspicious mainstream country debut this year with her album "Same Trailer Different Park."
"This first year for me has just been undescribable," said Musgraves, who set a record for nominations for a woman in her first year on the show.
Hosts Carrie Underwood and Brad Paisley got the show going on a jovial note as they took the stage with their opening skit, first joking about feuds in music. They also skewered Obamacare to a Nashville audience that roared with approval, and brought out the guys from the hit show "Duck Dynasty" and parodied Robin Thicke's "Blurred Lines."
Lee Brice's "I'd Drive Your Truck," about a fallen soldier whose father still drives his truck, won song of the year, and Little Big Town took its second straight vocal group of the year.
Swift later performed a somber, acoustic version of her hit "Red" with Vince Gill, Alison Krauss and Sam Bush and was given the CMA's Pinnacle Award. The award goes to artists who take country music to a worldwide audience. Garth Brooks is the only previous winner. He won in 2005.
The CMA brought a star-studded welcoming group out of stage for Swift that included George Strait, Rascal Flatts, McGraw, Urban, Faith Hill and Paisley - all of whom gave Swift a chance to open for them on the road a teenager. A video salute followed with appearances by Justin Timberlake, Julia Roberts, Carly Simon, Ethel Kennedy and Mick Jagger - whose appearance made Swift shout.
Swift recounted a call she got out of the blue from her Big Machine Records head Scott Borchetta when she was 16.
"He said, 'Can you be on the road in two days to open for Rascal Flatts,' and I immediately started screaming and said, 'This must be a miracle,'" she said. "He said, 'No, it's not a miracle. Eric Church got fired for playing too long."
She added: "You've made me feel so special right now, thank you."
Swift also is nominated for her third entertainer of the year award, the night's top honor.
Bryan and FGL weren't the only acts teaming up. Collaboration was the theme of the night as Strait and Alan Jackson joined together to salute the late George Jones with a rendition of "She Stopped Loving Him Today." Hunter Hayes and Jason Mraz took a tour of the Bridgestone Arena while performing "Everybody's Got Somebody But Me." And Brown and his band joined in on a growing hard-rock trend in country as Foo Fighter Dave Grohl joined the band on drums for new song high-powered "Day for the Dead".
And in one of the night's most anticipated moments, Kenny Rogers received the CMA's Willie Nelson lifetime achievement award and was saluted by Jennifer Nettles, Rucker and Rascal Flatts. Rogers sat on stage and mouthed along as Rascal Flatts sang "Just Dropped In (to See What Condition My Condition Is In)," the crowd helped Rucker sing "The Gambler" and Nettles and Rogers finished the tribute by singing "Islands in the Stream" together.
"It's been a hell of a month," Rogers said. "The (Country Music) Hall of Fame last week, this this week. I can't wait to see what's coming next week."