College openings in the United States increase mobility and COVID-19 incidence

School and college reopening-closure policies are considered one of the most promising non-pharmaceutical interventions for mitigating infectious diseases. Nonetheless, the effectiveness of these policies is still debated, largely due to the lack of empirical evidence on behavior during implementation. We examined U.S. college reopenings’ association with changes in human mobility within campuses and in COVID-19 incidence in the counties of the campuses over a twenty-week period around college reopenings in the Fall of 2020. We used an integrative framework, with a difference-in-differences design comparing areas with a college campus, before and after reopening, to areas without a campus and a Bayesian approach to estimate the daily reproductive number (R(t)). We found that college reopenings were associated with increased campus mobility, and increased COVID-19 incidence by 4.9 cases per 100,000 (95% confidence interval [CI]: 2.9–6.9), or a 37% increase relative to the pre-period mean. This reflected our estimate of increased transmission locally after reopening. A greater increase in county COVID-19 incidence resulted from campuses that drew students from counties with high COVID-19 incidence in the weeks before reopening (χ(2)(2) = 8.9, p = 0.012) and those with a greater share of college students, relative to population (χ(2)(2) = 98.83, p < 0.001). Even by Fall of 2022, large shares of populations remained unvaccinated, increasing the relevance of understanding non-pharmaceutical decisions over an extended period of a pandemic. Our study sheds light on movement and social mixing patterns during the closure-reopening of colleges during a public health threat, and offers strategic instruments for benefit-cost analyses of school reopening/closure policies.