The American actor and activist, who traveled by car from his residence on Lake Como, Italy, attended a private reception followed by a gala dinner in Geneva's Old Town.
"I'm very proud to be here and to be supporting the next President of the United States," Clooney told the reception, drawing applause.
"He deserves another four years to finish what he started," he added to shouts of "Yes" from donors.
Some $500,000 could be raised for Obama's campaign coffers as he battles to keep pace with the fundraising of his rival, Republican Mitt Romney, sources close to Obama's campaign said.
At least 100 American supporters paid $1,000 each to attend the champagne reception, while about 35 donors paid $15,000 a plate for the gourmet dinner with Clooney, they said.
"George Clooney, he spoke for about three to four minutes, very little. He just said we're doing good work and to keep it up," Walter Furth, a former chairman of Democrats Abroad Switzerland, told Reuters Television after the reception.
Michael Arnheiter, who was at the cocktail reception with his wife and two teenage children, said: "He told us what we've believed for the last several years, that the best opportunity for the United States to move forward is to re-elect Barack Obama.
"It was fun. My daughter got a nice picture with Mr. Clooney that will go right on Instagram tonight," he said.
"We loved hearing it, we're happy to be here and wrote a little bit of a check. We hope he wins because if not, we'll probably move to Europe," Arnheiter quipped.
Democrats Abroad Switzerland, the U.S. party's Swiss branch, said in a statement the event was expected to be the "single most important fundraising event" outside the United States for Obama's campaign. Some participants said it would be the Democrats' biggest fundraising event abroad to date.
Matthew Barzun, chairman of the Obama Victory Fund, and organizer Charles Adams, a Geneva-based American lawyer on the National Finance Committee of the campaign, spoke at the event.
Supporters willing to pay $5,000 got to have their photograph taken with the Hollywood star and director - who was not accompanied by his latest girlfriend Stacy Keibler.
"OUTSPENT AND OUTRAISED"
Clooney hosted a glitzy campaign fundraiser at his home in Los Angeles in May, raising nearly $15 million at the event where Obama called his endorsement of same-sex marriage a "logical extension" of his vision.
The Geneva fundraiser was a virtual carbon copy of one attended here by Clooney four years ago that raked in hundreds of thousands of dollars to help take Obama to the White House.
Obama's campaign to win re-election in the November 6 poll has struggled to match the enthusiasm of his 2008 run and compete financially with the hundreds of millions of dollars being raised by conservative outside groups known as super-PACs.
In July, Romney and his Republican Party raised $101 million, outpacing Obama for the third month in a row. Obama and the Democrats hauled in $75 million.
Democrats, eager to show they pay more heed to grassroots supporters than to the rich and powerful, on Monday imposed voluntary limits on donations to pay for their convention in Charlotte, North Carolina.
The limits have stressed out fundraisers and angered party insiders, who worry the new rules may alienate powerful allies they will need to re-elect Obama.
"We're being outspent and outraised. It's everyone to their battle stations, we've got to keep the playing field as level as possible," a participant at the Geneva fundraiser told Reuters. "Clooney has made himself available to an extent above and beyond the call of duty."
Tropical Storm Isaac forced Republicans on Sunday to postpone the start of the Republican National Convention being held this week in Tampa, Florida, where the party will officially nominate Romney as their candidate.
(Editing by Louise Ireland)
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