It has beaten the previous title-holder, 2003's Finding Nemo, to earn a whopping £194 million in ticket sales since it opened in May.
Shrek 2 is now the ninth biggest box office hit in North America ever, ahead of Lord of the Rings: The Two Towers.
The film, starring Cameron Diaz and Mike Myers, opens in the UK on 2 July.
The film was screened in America in 4,163 cinemas, making it the largest debut of all time.
The first Shrek movie made £151 million at the US box office and £258 million worldwide.
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