When people are in trouble, "they turn to friends who become their lifeline," said the FOX News commentator, who appeared after Clooney personally extended an invitation. "Who are their friends? You are."
"We have a choice," Clint Eastwood told the TV audience. "We can either look away or we can help."
Those helping on the air included former Presidents Bush and Clinton, and Madonna, singing John Lennon's "Imagine." Morgan Freeman told of a 60-year-old man in Sri Lanka who survived for two weeks before being found by rescuers. "Miracles do happen," he said. "You can be that miracle also."
Among those staffing the phones to answer 1-800-HELPNOW at a switchboard set up at the NBC Universal studios in Los Angeles were Brad Pitt (host Leno noted that he didn't even have time to shave), Johnny Depp, Matt Damon, Leonardo DiCaprio, Rob Lowe, Ben Affleck, Nicolas Cage, Tom Selleck and James Caan, among others.
Musical performers included Norah Jones, Sheryl Crow, Nelly, Annie Lennox, Stevie Wonder, Gloria Estefan, former Beach Boy Brian Wilson (who performed "Love and Mercy") and Lenny Kravitz (who played "Let Love Rule").
In pre-taped performances from London, Elton John delivered "Don't Let the Sun Go Down on Me" and Pink Floyd founder Roger Waters sang "Wish You Were Here," accompanied by Eric Clapton.
Also putting in appearances were Jamie Foxx, Naomi Watts, Drew Barrymore, Hugh Grant, Bruce Willis, James Woods, Annette Bening, Uma Thurman, Quentin Tarantino, Kelsey Grammer, Robert Downey Jr., Andy Garcia, Danny De Vito and Rhea Perlman.
The program closed with Diana Ross singing "Reach Out and Touch."