The University of Notre Dame evolved from a small Catholic boarding school in 1842 into an aspiring research university by 1967. Based primarily on original research in the University of Notre Dame Archives, this dissertation explains how science played the key role in this transformation. Notre Dame is arguably the highest profile Catholic university in the United States, and this study makes important contributions to understanding the history of American Catholic higher education. By fostering research in science, Notre Dame aspired to be ranked among the nation's leading research universities and most prestigious academic institutions in American higher education. The priest, botanist, and chemist Rev. Julius A. Nieuwland, C.S.C. conducted acetylene chemistry research that led to mass-produced poisonous gas during World War I and a catalyst for the efficient production of synthetic rubber by the 1930s. During World War II, Notre Dame's lay faculty scientists conducted secret research for the Manhattan Project and biological weapons. In the early Cold War, the University's administration attempted to build its research momentum in atomic physics and bacteriology and sought funding to establish other "steeples of excellence" in research. A prominent figure in this history is Rev. Theodore M. Hesburgh, C.S.C. who served as the University's president from 1952 to 1987. By the 1960s, the University was a modern Catholic research university adapting to the world of science, but Hesburgh remained wary of the influence of the military-industrial-academic complex. Aspects of the University's religious identity raised issues relative to federal funding eligibility and were addressed by transferring institutional ownership and control to a lay-clerical board of trustees in 1967. That same year, Notre Dame issued a declaration of its academic independence as a research university with the Land O'Lakes Statement, and this changed the University's relationship with the Catholic Church to a less formal one. This dissertation raises challenging questions regarding the relationship between faith and science.