The national police force, the Garda Siochana, said a lone man drove into the brewery - a Dublin landmark and top tourist attraction - on Wednesday and hitched his truck to a fully loaded trailer awaiting delivery to city pubs.
Diageo PLC, the drinks company that owns Guinness, said the brewery had never suffered such a large-scale theft before in its 248-year history.
Police said the raider took 180 kegs of Guinness stout, 180 kegs of U.S. lager Budweiser and 90 kegs of Danish beer Carlsberg. Guinness brews both of those brands under license for sale in Ireland.
The Garda Siochana declined to say whether the theft had been captured by closed-circuit surveillance cameras. No description of the suspect was issued, suggesting that nobody got a good look at him.
Each keg holds about 88 British-sized pints, the most common serving size in Ireland equivalent to 20 ounces (568 milliliters) each. The total theft involves 39,600 pints with a retail value exceeding €160,000 (US$235,000).
Police said it would be difficult for the thief to sell the stolen beer without attracting attention, unless he has criminal associates who own a network of pubs.
In the past, the outlawed Irish Republican Army and other gangs all have highjacked truck shipments of alcoholic beverages and cigarettes for resale in pubs run by sympathizers or friends. Those raids typically happen in rural areas, never in the center of Dublin.
Customs agents say it is extremely common for pubs to be selling stolen or smuggled cigarettes and alcohol, particularly counterfeit-labeled supplies of vodka, to avoid paying hefty taxes on both categories of goods.
The Republic of Ireland, a country of 4.2 million, has more than 10,000 pubs and bars. The Guinness brewery in Dublin is the biggest supplier, producing more than 5 million kegs annually.