The telecast will take place on the Universal Studios lot in Hollywood, California, as well as New York City's Times Square and Nashville's Grand Ole Opry. Country crooner George Straight is also set to perform from the Majestic Theater in San Antonio, Texas.
In a statement released to ET, Clooney explained why he got involved in the Hurricane relief telethon.
“As Americans and as human beings we have a responsibility to look out for one another," the statement read. "I'm proud to lend my voice and help in any way I can. For as long as it takes."
Other stars confirmed to either appear live or in a pre-taped segments are Jamie Foxx, Tori Kelly, Karlie Kloss, Rob Lowe, Matthew McConaughey, Dennis Quaid, Kelly Rowland, Adam Sandler, Ryan Seacrest, Michael Strahan and Blake Shelton.