Witherspoon won an Oscar for her portrayal of country music icon June Carter Cash in the film "Walk the Line."
Other celebrities ready to hand out prizes at Wednesday night's event are Erin Andrews, Josh Dallas, David Freese, Ginnifer Goodwin, Kellan Lutz, Eric Stonestreet and Emily VanCamp. Brad Paisley and Carrie Underwood are to serve as co-hosts of the awards ceremony at the Bridgestone Arena.
Slated to perform are Jason Aldean, The Band Perry, Luke Bryan, Eric Church, Sara Evans, Faith Hill, Lady Antebellum, Miranda Lambert, Martina McBride, Scotty McCreery, Taylor Swift, Thompson Square, Keith Urban, Chris Young and Zac Brown Band.
Kenny Chesney and Grace Potter also are to sing their hit collaboration "You and Tequila," and Vince Gill, Paisley and Urban will perform a tribute to Glen Campbell, who recently announced he is suffering from Alzheimer's disease.
Rascal Flatts and Natasha Bedingfield will sing their hit "Easy;" Lionel Richie will perform duets with Little Big Town, Rascal Flatts and Darius Rucker; and Blake Shelton will be joined by Kenny Loggins for a rendition of "Footloose," organizers said.