The scheme, in Atlanta, will be a challenge because it sits directly opposite Richard Meier's High Museum of Art, recently extended by Renzo Piano.
The London-based architect will design 'One Museum Place', a mixed-use scheme including a contemporary art gallery for the High Museum.
Chipperfield was the only foreign architect selected for the commission's final interview process. The appointment is further evidence of his burgeoning reputation in the US.
The 1,394m 2gallery will provide 'highly flexible space' for temporary shows, including those by resident artists.
The project will also include flats, a private dining club and shops.