(CNN) -- For 45 years, Jerry Lewis and the Muscular Dystrophy Association's annual Labor Day fundraiser have been synonymous, so much so that it's now known as the Jerry Lewis MDA Telethon, in honor of the comic's tireless efforts.
But this September, the 85-year-old star will don his tuxedo to entertain the masses and help "Jerry's Kids" for the last time, the charity announced Monday.
"As a labor of love, I've hosted the annual telethon since 1966," Lewis said in news release issued by the Muscular Dystrophy Association. "And I'll be making my final appearance on the show this year, by performing my signature song, 'You'll Never Walk Alone.' "
Lewis hit it big at age 20 in 1946, teaming up with Dean Martin to become one of the most popular comedy partnerships in history. Together, they headlined thousands of sold-out performances, 16 hit movies and two dozen top-rated television shows.
After the break-up of the Martin and Lewis team, Lewis made a successful solo career. In 1959, he signed a seven-year, $10 million contract with Paramount -- at the time, the largest contract ever between a studio and performer.
His solo film career included classics such as "The Nutty Professor," "The Bellboy" and "The Geisha Boy."
Still, for several generations since, Lewis has been known as much as a philanthropist as a movie star. That's because of his work with the Muscular Dystrophy Association, a nonprofit dedicated to curing that disease, ALS and related ailments as well as providing support, education and other services.
Lewis joined the cause in the early 1950s, and he gave it star power in 1966 when he became the host of what would be the charity's first of many telethons over Labor Day weekends.
In between occasional songs, comic bits and passionate pitches for people to donate, his biggest challenge was keeping the variety show lively and engaging for as long as 21.5 hours straight. Scores of television stations across the country picked up the program, while volunteers stood by to take calls from people pledging donations.
The 2010 edition, for instanced, raised $58,919,838 after performances by the likes of acrobatic dancers from Cirque du Soleil, "American Idol's" David Archuleta and a host of comedic performers. Still, throughout the plethora of acts, the one constant over 900 hours of programming has remained Lewis.
This year's event, on September 4, will be shorter than many of years past at six hours. Still Lewis promised that it "will be spectacular, and I'm thrilled to be a part of it."
Even as he steps down as host, Lewis said he will continue to serve as national chairman of the Muscular Dystrophy Association. The group's president, Gerald Weinberg, thanked the comic for remaining committed to the cause, as well as for his efforts over the years.
"All of us who've been privileged to work beside him, and the hundreds of thousands throughout the world affected by the myriad of muscle diseases MDA battles, will acknowledge in our hearts forever the unrivaled role Jerry has played in our lives and the lives of all Americans," Weinberg said in the news release.