The evaluation of COVID-19 policy effectiveness on university campuses, particularly in mitigating spread to neighboring cities (i.e., “campus spill-over”), is challenging due to asymptomatic transmission, biases in case reporting, and spatial case reporting limitations. Wastewater surveillance offers a less biased and more spatially precise alternative to conventional clinical surveillance, thus providing reliable data for university COVID-19 policy evaluation. Wastewater surveillance data spanning the academic terms from Fall 2020 through Spring 2022 was used to evaluate the impact of university COVID-19 policies. During the campus closure to external visitors (09/21/2020–9/15/2021), campus viral concentrations and variant compositions were dissimilar from those of the host and neighboring cities (MAPE = 0.25 ± 0.14; Bray–Curtis = 0.68 ± 0.1, respectively), indicating relative isolation of the campus from its surroundings. Upon the campus reopening to visitors (9/15/2021–2/27/2022), the viral concentrations and variant compositions matched more closely with the host and neighboring cities (MAPE = 0.21 ± 0.1; Bray–Curtis = 0.14 ± 0.08, respectively). Furthermore, post-lifting of campus and state mask mandates (2/27/2022–6/12/2022), the campus, host and neighboring city viral concentrations and variant compositions became indistinguishable (MAPE = 0.06 ± 0.02; Bray–Curtis = 0.07 ± 0.05, respectively). This data suggests that university COVID-19 policies effectively prevented campus-spill over, with no significant contribution to COVID-19 spread into the surrounding communities. Conversely, it was the surrounding communities that led to the spread of COVID-19 onto the campus. Therefore, wastewater surveillance proves instrumental in monitoring COVID-19 trends in surrounding areas, aiding in predicting the impact of easing campus restrictions on campus health.