Campbell announced in June 2011 that he had been diagnosed with Alzheimer’s disease and that it was in its early stages at that time.

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Glen Campbell, the multiple Grammy-winning country-pop singer, guitarist and TV personality whose half-century career was capped by a singular last act after he went public with his advancing Alzheimer’s disease, has died. He was 81.

Possessed of a crystalline tenor voice, boyish good looks and a high-wattage smile, Mr. Campbell sold more than 45 million records and was known for a signature string of ’60s and ’70s country-music hits that included “Gentle on My Mind,” “Wichita Lineman” and “Rhinestone Cowboy.”

Mr. Campbell began to slowly draw the curtain on his prolific career after announcing that he had been diagnosed with Alzheimer’s in 2011, a battle that inspired a farewell tour, documentary and a heartbreaking final album, “Adios,” released in 2017.

Mr. Campbell’s death was announced Tuesday in a post on his official website and social-media accounts.

“It is with the heaviest of hearts that we announce the passing of our beloved husband, father, grandfather, and legendary singer and guitarist, Glen Travis Campbell, at the age of 81, following his long and courageous battle with Alzheimer’s disease,” the statement said.

Born in Billstown, a tiny community near the town of Delight, Arkansas, he was the seventh son of a seventh son, the child of sharecropper John Wesley and Carrie Dell Campbell, who would go on to have several more children. By all accounts, his early life was one of severe poverty that included picking cotton in the fields alongside his brothers. The seeds of his career were planted at the age of 4 when he received a guitar that had been ordered from a Sears, Roebuck & Co. mail-order catalog.

By age 6, he was skilled enough to appear on local radio stations, and by 10th grade he would quit high school to pursue a music career full time. By the time he was 20, he had joined his uncle’s band — the Albuquerque-based Sandia Mountain Boys — where he would hone his skills before striking out on his own to form Glen Campbell and the Western Wranglers in 1958.

In his 20s, Mr. Campbell, who had come West to Los Angeles to seek stardom, flourished as part of the Wrecking Crew, the fabled, though mostly unknown to the public, collective of studio and session musicians who played behind some of the biggest names in the music business.

He would become a longtime resident of the Los Angeles area. In this early stage in his career, he was sought after as a virtuoso guitarist, and his brisk, confident guitar work was part of, among many others, Elvis Presley’s “Viva Las Vegas,” The Monkees’ “Last Train to Clarksville,” and “Pet Sounds” by the Beach Boys, with whom he would briefly go on tour as a substitute for Brian Wilson.

Campbell’s career started to move center stage — or at least further to the front of it — with a few modest hits beginning with “Turn Around, Look at Me,” a 1961 single he recorded for Crest Records; “Kentucky Means Paradise,” a 1962 tune recorded with the Green River Boys; and “Swingin’ 12 String Guitar” as part of the Folkswingers in 1963.

His big breakthrough, though, came in 1967 when his recording of the John Hartford tune “Gentle on My Mind” hit the No. 1 spot on the country charts and the Billboard Top 40 and earned Mr. Campbell a Grammy.

“By the Time I Get to Phoenix” brought a second Grammy and debuted his fruitful pairing with songwriter Jimmy Webb — one of those made-in-heaven singer-songwriter matches that helped make legends of both men. Webb also wrote “Galveston” and the iconic “Wichita Lineman.”

Mr. Campbell’s first two hits earned him the Country Music Association’s 1967 Entertainer of the Year award. “By the Time I Get to Phoenix” earned him three more Grammys, including album of the year in 1968.

Like Bobbie Gentry, with whom he recorded two Top 40 duets, and his friend Roger Miller, Mr. Campbell was a hybrid stylist, a crossover artist at home in both country and pop music.

“A change has come over country music lately,” he explained in 1968. “They’re not shuckin’ it right off the cob anymore. Roger Miller opened a lot of people’s eyes to the possibilities of country music, and it’s making more impact now because it’s earthy material, stories and things that happen to everyday people. I call it ‘people music.’ ”

It wasn’t long after that the rising star with the wide smile, dimpled chin and sideburns would add television-show host to his résumé, first as co-host of a 1968 summer replacement for “The Smothers Brothers Comedy Hour,” and the next year as host of “The Glen Campbell Goodtime Hour,” a CBS prime-time variety show that aired until 1972.

Along the way he appeared on the big screen, too — most notably alongside John Wayne in the original 1969 version of “True Grit” (Mr. Campbell played La Boeuf, the role reprised by Matt Damon in the film’s 2010 remake), and as a Vietnam veteran returning stateside in “Norwood” (1970).

The 1970s found Mr. Campbell’s music reaching a wider audience, evidenced by songs such as “Rhinestone Cowboy,” which hit No. 1 on Billboard’s Hot 100, country and adult contemporary charts in 1975, followed two years later by his second and final No. 1 hit, “Southern Nights,” written by revered New Orleans musician Allen Toussaint.

The ’80s were a country song gone awry for Mr. Campbell, a decade defined less by his creative output than by his battles with drugs and alcohol and his tempestuous, on-again, off-again affair with singer Tanya Tucker, who was half his age. By the mid-1990s he’d taken up residence at the Glen Campbell Goodtime Theatre in Branson, Mo., where he performed regularly. His output from these years skewed heavily toward Christmas albums, gospel records and best-of compilations.

In 2005 Mr. Campbell was inducted into the Country Music Hall of Fame. Three of his songs have been inducted into the Grammy Awards Hall of Fame: “Wichita Lineman” (in 2000), “By the Time I Get to Phoenix” (2004) and “Gentle on My Mind” (2008). Campbell received a Grammy Lifetime Achievement Award in 2012.

He began a late-career renaissance in 2008 through his collaboration with producer and songwriter Julian Raymond, who persuaded him to record a diverse batch of songs by younger, hipper artists, including Green Day, Tom Petty, the Replacements and U2.

Mr. Campbell released “Ghost on the Canvas” in 2011, following that with a final stretch of concerts. The “Goodbye Tour,” which pushed into 2012, was the subject of the James Keach documentary “Glen Campbell: I’ll Be Me,” released in 2014 — the same year Mr. Campbell moved into an Alzheimer’s treatment facility, after listing his Malibu home for sale the previous year. With the help of his children and admiring friends such as Willie Nelson, he released a final album in the spring of 2017, titled — simply — “Adios.”

His farewell tour and the accompanying film elicited an emotional outpouring. Rejecting the shame and secrecy that sometimes attend Alzheimer’s, Mr. Campbell turned into an advocate for the disease and was staunchly public about his affliction; audiences cheered him even as he struggled to remember his lyrics on stage.

In the film, former President Bill Clinton saluted Mr. Campbell’s actions, saying his advocacy on behalf of those with Alzheimer’s might ultimately outstrip his contributions to music as his most lasting legacy.

Yet even as his disease progressed, he retained a deep musical fluency. He would forget the words to songs, his documentarian later said, but not the music. He could still hit the notes.

Also featured in the film was the song “I’m Not Gonna Miss You,” which Mr. Campbell had written and recorded with Raymond.

Like the Goodbye Tour, the song is unique in the country canon. Stark, specific and unsentimental, its few simple lines convey profound loss, both for Alzheimer’s sufferers and those who love them. It opens with, “I’m still here/ But yet I’m gone.”