Depp was the top winner at the ceremony, which aired Tuesday, receiving awards for favorite male movie star, favorite action star and favorite on-screen match-up with "Pirates of the Caribbean: Dead Man's Chest" co-star Keira Knightley.
The actor accepted his awards via satellite from London.
Degeneres took home the awards for favorite funny female star and favorite talk show host. Underwood was named favorite female singer and given the favorite country song prize for "Before He Cheats. Flatts won favorite remake and favorite song in a movie for "Life is a Highway."
"Pirates" was named favorite movie and favorite movie drama. ABC's "Grey's Anatomy" was named favorite TV drama and CBS' "Two and a Half Men" was labeled was favorite TV comedy. NBC's "Heroes" was given favorite new TV drama honors.