Cret was born in Lyons, France, on October 23, 1876, the son of Paul Adolphe and Anna Caroline (Durand) Cret. He attended a Lycee in Bourg and studied architecture at the L'Ecole des Beaux-Arts in Lyonsand the L'Ecole des Beaux Arts in Paris, which was widely recognized as Europe's leading architectural academy at that time. At the Paris school, he graduated in 1903, he was awarded the Rougevin Prize and the Grand Medal of Emulation, both in recognition of his remarkable skill as a draftsman. In 1903 he was invited to teach architecture at the University of Pennsylvania, where he remained until his retirement in 1937.
The University of Pennsylvania appointed Cret as an architecture critic in 1903, after which Cret remained closely associated with the United States and the City of Philadelphia. He served in the French army during World War I, but otherwise spent most of his time in the United States. Cret became a United States citizen in 1927. During the 1930s, he designed a significant number of federal facilities, including the 1932 Federal Reserve Bank building in Washington, D.C. Cret also worked as architect for many engineering projects, most notably the Benjamin Franklin Suspension Bridge in Philadelphia.
During his long tenure at Penn, Cret was recognized as one of the foremost practitioners of the "Beaux-Arts" style, and his work left a lasting impact on the built environment of the United States, forming a bridge between the end of Beaux-Arts historicism and the rise of modernism. Cret's early buildings--among them the Pan American Union Building in Washington (1907-10), the Indianapolis Public Library (1917), and the Detroit Institute of Arts (1927)--demonstrated a refined classicism that represented the best traditions of the Beaux-Arts style. By the late 1920s, however, he began to experiment with a new, radically stripped-down classicism, exemplified by his Folger Shakespeare Library (1930-37) in Washington, that was more attuned to growing modernism. In 1937 ill health forced him to resign from the University of Pennsylvania. His last important work was the Federal Reserve Bank (1935-37) in Philadelphia. Paul Philippe Cret died of a heart ailment in Philadelphia on September 8, 1945.