C. Clark Zantzinger was born in Philadelphia, the son of Margaret Shippen (Buckley) and the architect Clarence C. Zantzinger
. Like his father, the younger Zantzinger attended St. Paul's School in Concord, NH (graduating in 1922), then Yale, where he earned a B. A. in 1926, and finally the University of Pennsylvania, where he completed a B.Arch. and then an M.Arch., in 1929 and 1930, respectively. While at Penn, Clark Zantzinger won the Arthur Spayd Brooke Memorial Prize Gold Medal and the Paul Philippe Cret Prize in 1929-30. He also studied at the Ecole des Beaux Arts in Fontainebleau, France, earning a diploma after a summer of study in 1928.
Zantzinger started his career as a draftsman in his father's firm, Zantzinger & Borie, working there between 1928 and 1933. In 1935, he formed a partnership with H. Martyn Kneedler, a Penn classmate who had also studied at the Fontainebleau Ecole, and Henry D. Mirick, who had been in the next class at Penn.
Zantzinger joined the national AIA the following year. He continued to practice with the firm until his retirement in 1969, the same year he was made a fellow of the AIA. In 1973 Zantzinger transferred his Chapter membership to Maine.
Zantzinger was a member of the board of directors of the Philadelphia Chapter of the AIA in the 1950s. He served on the Philadelphia Mayor's Council on Penn Center and the Citizens' Council for City Planning in the same period, when redevelopment was changing the face of the downtown. He was also active in Philadelphia charitable and civic organizations. He was a trustee of the Episcopal Hospital from 1937 until 1978, serving as the board's vice president from 1968 until 1971. Zantzinger also was a director of the Fairmount Park Art Association from 1955 until his death, and that body's president between 1969 and 1980. During his presidency, the organization published Sculpture of a City: Philadelphia's Treasures in Bronze and Stone (New York: Walker Publishing Co., 1974), an important document of the city's public art. He promoted the acquisition of Jacques Lipchitz's public sculpture, Government of the People, derogatorily described by then-mayor Frank Rizzo as looking as if "plasterers had dropped a load of plaster."