Lewis, 85, has been the MDA's national chairman since the early 1950s and has hosted the Labor Day Muscular Dystrophy Association telethon since 1966.
He announced in May that he was retiring as host of the telethon that has become synonymous with his name. But Lewis added that he planned to make his final appearance on this year's Sept. 4, show and planned on continuing to serve as MDA's national chairman.
MDA Chairman of the Board R. Rodney Howell said in a statement that Lewis "will not be appearing on the telethon" and "we will not be replacing him as MDA national chairman."
Howell added that Lewis "is a world-class humanitarian and we're forever grateful to him for his more than half century of generous service to MDA."
The statement did not provide any further explanation for the moves, and calls to the Tucson, Ariz,-based nonprofit weren't immediately returned Wednesday night. Representatives for Lewis, a publicist and a manager, also did not immediately respond to messages left for comment.
Lewis, a Las Vegas resident, has in recent years battled a debilitating back condition, heart issues and the crippling lung disease pulmonary fibrosis.
MDA officials said more than $1 billion has been raised during Muscular Dystrophy Association telethons over the years and a national network of some 200 hospital-affiliated clinics has opened since Lewis became involved in the telethon.
Lewis' first live Labor Day weekend telethon in 1966 was broadcast by a single New York City television station. It raised more than $1 million in pledges.
The telethon moved from New York to Las Vegas in 1973 and had stints in Los Angeles before returning in 2006 to Las Vegas.
Last year's Jerry Lewis MDA Telethon aired from the South Coast hotel-casino on the Las Vegas Strip and was broadcast by more than 170 stations. It raised almost $59 million to fund research to find a cure for muscular dystrophy and ALS, or Lou Gehrig's disease.
The live telethon usually lasts 21 1/2 hours. Sometimes Lewis would sing or tell lighthearted jokes. He introduced guests and other performers like a ringmaster. Sometimes, he turned serious and shared stories of people afflicted by the disease or who were helped by the association. All the while, he urged donors to contribute while a tote board rang up pledge totals.
Some telethon moments have made history.
In Las Vegas during the 1976 telethon, Lewis was reunited by Frank Sinatra with Dean Martin, with whom the comedian had an acrimonious split 20 years earlier. The famous entertainer best known for his slapstick humor first teamed with Martin in the 1940s to play nightclubs and television shows and to make a series of comedy films.