In March 2020, New York City (NYC) experienced an outbreak of coronavirus disease 2019 (COVID-19) which resulted in a 78-day mass confinement of all residents other than essential workers. The aims of the current study were to (1) document the breadth of COVID-19 experiences and their impacts on college students of a minority-serving academic institution in NYC; (2) explore associations between patterns of COVID-19 experiences and psychosocial functioning during the prolonged lockdown, and (3) explore sex and racial/ethnic differences in COVID-19-related experiences and mental health correlates. A total of 909 ethnically and racially diverse students completed an online survey in May 2020. Findings highlight significant impediments to multiple areas of students' daily life during this period (i.e., home life, work life, social environment, and emotional and physical health) and a vast majority reported heightened symptoms of depression and generalized anxiety. These life disruptions were significantly related to poorer mental health. Moreover, those who reported the loss of a close friend or loved one from COVID-19 (17%) experienced significantly more psychological distress than counterparts with other types of infection-related histories. Nonetheless, the majority (96%) reported at least one positive experience since the pandemic began. Our findings add to a growing understanding of COVID-19 impacts on psychological health and contribute the important perspective of the North American epicenter of the pandemic during the time frame of this investigation. We discuss how the results may inform best practices to support students' well-being and serve as a benchmark for future studies of US student populations facing COVID-19 and its aftermath.