The charity organisation has now confirmed that Lythgoe, Sweeney, Entertainment Tonight's Nancy O'Dell and journalist Jann Carl will replace Lewis as co-hosts for the Labour Day weekend telecast.
Celine Dion, Lady Antebellum, Martina McBride and Jordin Sparks have been lined-up as musical guests, while American Idol judges Jennifer Lopez, Steven Tyler and Randy Jackson and the cast of The View will also make special appearances.
Telethon producer Lee Miller touted the show's all-star line-up, saying: "Songs and appeals by these outstanding artists, as well as extraordinary Penn & Teller magic and so much more, undoubtedly will captivate tens of millions of viewers.
"Then, when America sees and hears from remarkable families served by MDA, people once again will find it near impossible to not respond generously."
This year's MDA telethon will air over a six-hour stretch of primetime on Sunday, September 4, marking a change from the usual 21-hour format.