People reports that the Black Eyed Peas singer will kick off the three-hour broadcast scheduled tonight (September 2) at 8pm ET.
The Black Eyed Peas singer will reportedly be performing his song 'This Is Love' with Eva Simons and MDA Los Angeles Goodwill Ambassador Lucas Cook.
"MDA has been helping children and adults for more than 50 years, and I am pleased to collaborate with them to help save lives," the hip-hop artist said of the event.
"I am on a mission to transform the lives of young people who need extra support and really am honoured to perform on the show - and it was important for me to include Lucas and other MDA kids in our performance."
Set up as a charity to help fight muscular dystrophy, the telethon will also feature performances by Carrie Underwood, Carole King, Gavin DeGraw, and Pitbull.
The show will be streamed live on the MDA website.
Watch will.i.am's video for 'This Is Love' below: