The COVID-19 pandemic has overturned daily routines across the entire planet. And newly arrived college students in the fall of 2019 were no exception. In addition to adjusting to the college transition, they had to cope with the multiple consequences of the pandemic’s first wave (e.g., confinement, quarantine, physical distancing, remote learning, job loss). To date, it is unknown how this experience has affected students, and particularly the most vulnerable. The main objective of this study was to examine, from a stress and coping perspective, how college students with and without disability experienced the first COVID-19 wave. A longitudinal study using online surveys was conducted in a sample of 1,465 students (mean age = 18.2) attending college in the province of Québec (Canada), of whom 42% disclosed a disability (i.e., ADHD, mental health disorder, or learning problem) at college entry. Exposure to COVID-19 varied according to disability type, study region, and study program. After controlling for exposure, students’ initial adjustment to college, and high school GPA, students with a disability, and particularly those presenting a mental health disorder, experienced greater stress and had greater difficulty coping with the situation compared to students without a disability. Generally, girls and students attending a college in an urban area were more affected by the pandemic. Results are discussed with a view to designing preventive measures for at-risk students who enter college during a pandemic.