In the hopes of advancing his own studies, Moore, with the aid of the GI Bill, enrolled at Princeton University upon discharge. He arrived there in 1954 where he immediately formed important relationships with fellow students who would remain lifelong friends and collaborators, including William Turnbull, Jr., Donlyn Lyndon, Richard Peters, and Hugh Hardy. Moore's work at Princeton was influenced by its Dean Jean Labatut, professors Enrico Peressutti, George Rowley, and especially Louis Kahn, for whom he served as a Post Doctoral Teaching Assistant. Moore completed a Master's Degree and Ph.D. in only three years, writing his dissertation on Water and Architecture.

Graduating in 1957, Moore returned to the Bay Region, where he commenced a remarkable 35-year odyssey of design, teaching, writing, collecting, and travel. Moore would teach and lead departments at UC Berkeley, Yale, UCLA, and the University of Texas, he would establish seven architecture firms, and write a dozen books, all while indefatigably traveling the world, frenziedly amassing an exuberant collection of folk art and toys.

While at Berkeley, Moore commenced a collaboration with William Turnbull, Jr., Donlyn Lyndon, and Richard Whitaker. Their firm, MLTW, soon began producing work of international distinction, including Moore's own house at Orinda; small houses and cabins along the California coast, and, most notably, the Sea Ranch Condominium in Sonoma County. (This structure would later be recognized with the prestigious AIA 25 Year Award.)

When Moore accepted the chairmanship of the Yale School of Architecture (later to become Dean when the department was reorganized), he continued his collaborations with the Berkeley group, establishing a satellite office in New Haven known as MLTW:Moore/Turnbull. Eventually, however, Turnbull established his own practice, whereupon Moore established a new firm in New Haven, Moore Grover Harper, with William Grover and Robert Harper. This firm eventually grew into Centerbrook Architects and Planners, ultimately settling in Centerbrook (Essex), Connecticut, where today it continues its work.