The senators picked the grapes with Western ally Saakashvili and then trampled them into pulp in a vat at the Georgian leader's country cottage on Thursday, video images released by the presidency showed (click here to watch the video).
"Let's get to work," McCain said as he started to fill a basket with grapes.
McCain, Lieberman and Graham were serenaded by Georgian folk singers in traditional costumes and made a toast with a powerful grape-derived local spirit called 'chacha'.
"To you, Mr President, to our friendship, to our alliance, to your health," Lieberman said before clinking glasses with Saakashvili.
Visiting Polish and Swedish foreign ministers Radoslaw Sikorski and Carl Bildt on Wednesday also harvested grapes at the charismatic Georgian president's vineyard in the country's rural eastern region of Kakheti (read more and watch video here).
The two top diplomats held on to each other and danced up and down merrily in the vat as they crushed the grapes in front of a grinning Saakashvili, video footage on the presidency's website showed.
"Is this ever done by two foreign ministers?" Sikorski asked as they stepped into the vat wearing rubber boots.
Georgia has been seeking to promote its wine internationally after a ban by Russia in 2006 cut off its biggest foreign market amid tensions with Moscow that would erupt into war two years later.
Georgia claims to be the "cradle of wine", citing archaeological finds which suggest that viticulture may have begun there as early as 8,000 years ago.