Depp joined "Pirates" producer Jerry Bruckheimer to accept the Golden Popcorn trophy.
"This is the man who did it all right here, Johnny Depp," Bruckheimer said. "Without him, we wouldn't be here."
PHOTO ESSAY: The 2007 MTV Movie Awards/a>
"I'd like to thank this man and Disney for not firing me first," Depp quipped.
Other big winners during the live broadcast from the Gibson Amphitheater included Mike Myers, who won the MTV Generation Award, and Sacha Baron Cohen, who collected two trophies.
Cohen earned the comedic performance prize for his starring turn in "Borat: Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan."
"Unfortunately, Borat can't be here tonight," he joked. "He's been feeling the pressures of fame and had to check himself into rehab."
Cohen also claimed best-kiss honors for his smooch with Will Ferrell in "Talladega Nights: The Ballad of Ricky Bobby." The two comedians shared a long, passionate kiss — culminating in a roll-around-on-the-floor makeout session — as they accepted their awards.
The movie prizes were almost upstaged by a star who wasn't nominated for any: Paris Hilton.
The heiress, who must report to Los Angeles County Jail by midnight Tuesday, caused a commotion when she arrived on the ruby carpet outside the amphitheater. Wearing a ruffled black dress and dazzling jewels, she flashed her trademark coy smile as she posed for photos and talked with reporters.
"I'm really scared but I'm ready to face my sentence," she said. "Even though this is a really hard time, I have my family, my friends and my fans to support me, and that's really helpful."
Host Sarah Silverman cracked a crude joke at Hilton's expense to open the show. When the camera panned to Hilton, she was not smiling.
Then the focus turned to films. MTV's irreverent mix of honors includes prizes for best fight and best villain, plus awards for aspiring filmmakers.
Jack Nicholson was the winning villain, capturing the Golden Popcorn trophy for his mobster role in "The Departed." The fight prize went to Gerard Butler, who battled "The Uber Immortal" in the epic "300."
The breakthrough performance prize went to 9-year-old Jaden Smith, who starred opposite his father, Will Smith, in "The Pursuit of Happyness." He accepted his award by video from Toronto with his dad by his side and his mom behind the camera.
The two-hour program was punctuated by musical performances. Rihanna and Jay-Z paired up on her new song "Umbrella," and soul songstress Amy Winehouse sang her megahit, "Rehab."
The 16-year-old awards show unveiled two new categories Sunday: best movie spoof and best summer movie you haven't seen yet. Andy Signore, a filmmaker from Pennsylvania, won for "United 300," a hybrid spoof of "300" and "United 93."
"Transformers," due July 3, was named the best as-yet-unseen summer film.
MTV viewers voted by telephone, text message and Internet to choose the winners in all categories.