Alicia Keys opened proceedings with a performance of her hit Prelude to a Kiss, before Clooney addressed a TV audience of millions with an impassioned plea for help.
Referring to the earthquake that killed tens of thousands and devastated the Caribbean nation earlier this month (Jan10), he said, "This is a tragedy that reaches across all borders and all boundaries and demands our attention, our help and our compassion as fellow human beings.
"The Haitian people need our help. They need to know they're not alone, they need to know that we still care."
Clooney then introduced the audience to a host of stars manning telephones in the Los Angeles studio, including Ben Affleck, Daniel Day-Lewis, Mel Gibson, Colin Farrell, Meg Ryan and Ringo Starr.
Friday's event is split between Los Angeles and New York, where Wyclef Jean is hosting.
Those who wish to donate can do so by visiting Hopeforhaiti.org.