The £138m Tate Modern was their biggest work when they won the contract in 1995.
Jacques Herzog and Pierre de Meuron will share the prize, which awards living architects whose work combines "talent, vision and commitment".
They are best known for their conversion of the Bankside power station on the River Thames into the Tate Modern gallery, which has been described as a "cathedral of cool".
The prize rewards "consistent and significant contributions to humanity and the built environment through the art of architecture." They also receive $100,000 (£70,000).
The £138m Tate Modern was their biggest work when they won the contract in 1995.
It combines the existing building with some modern touches such as a glass roof.
"It has its moments of ambiguity," Herzog said.
"We found a very strong instrument to deal with architecture and urbanism also."
Herzog predicted in 1998 that the Guggenheim museum in Bilbao, Spain, would "suffer badly" in comparison.
The chairman of the Pritzker jury, J Carter Brown, said the duo combine "the artistry of an age-old profession with the fresh approach of a new century's technical capabilities.
"One is hard put to think of any architects in history that have addressed... architecture with greater imagination and virtuosity."
'Extraordinary'
Another jury member, Houston architect Carlos Jimenez, cited their capacity to astonish.
"They are able to transform rather ordinary shapes, conditions or materials into something that becomes truly extraordinary," he said.
The pair were both born in 1950 and met in elementary school, where they played with building blocks together.
They formed a company in 1978 and now employ almost 150 people.
Forthcoming projects include the new MH de Young
Memorial Museum in San Francisco, an expansion of the
Walker Art Center in Minneapolis and the Prada headquarters in
New York.
They will also work on a new port in Tenerife, a large cultural hall in Barcelona and a $25m (£17.6m) hi-tech house for Californian venture capitalist Richard Kramlich.
They will be given the award during a ceremony on 7 May on American founding father Thomas Jefferson's estate in Charlotteville, Virginia.
The prize was established in 1979 by the Pritzker family, who run the Hyatt hotel chain, as a way to honour living architects and inspire greater creativity.
The first winner was American Philip Johnson, and the only other time the prize has been shared was in 1988 when it went to Brazilian Oscar Niemeyer and late American Gordon Bunshaft.
Last year's winner was Dutch architect Rem Koolhaas.
Herzog and de Meuron are the first Swiss citizens to win the award.