Greek authorities say armed robbers have seized dozens of items on display at the museum in Ancient Olympia, the birthplace of the Olympics in southern Greece, after tying up an employee.
Greece's Culture Minister Pavlos Geroulanos submitted his resignation after the robbery, state television reported.
Police and museum authorities did not have an immediate account of the items taken from smashed display cases, but local authorities and police said about 60 artifacts are estimated to have snatched.
Sporting authorities are to hold a ceremony at the museum on May 10 to light the Olympic flame for the London Games.
Friday's robbery is the second major museum theft in the past two months in Greece. In January, thieves made off with art works by 20th century masters Pablo Picasso and Piet Mondrian from the country's National Gallery in central Athens.
In that pre-dawn heist, the burglars also took a pen and ink drawing of a religious scene by Italian 16th century painter Guglielmo Caccia.
A fourth work by Mondrian also was removed from the National Art Gallery in one of the best-guarded areas of central Athens, but the thieves abandoned it as they fled. No arrests have been made.