Understanding factors that foster resilience and buffer against the negative psychological impact of COVID-19 is critical to inform efforts to promote adjustment, reduce risk, and improve care, particularly for adolescents with neurodevelopmental disorders. This prospective longitudinal study addresses this gap by investigating the impact of the COVID-19 pandemic on adolescents' mental health and substance use, and by assessing specific positive coping strategies among adolescents with and without attention-deficit/hyperactivity disorder (ADHD). Using multi-group autoregressive cross-lagged path models, the present study explored the reciprocal influence of positive coping behaviors on multiple adjustment outcomes including mental health symptoms, substance use, stress, and worry. Participants included 238 adolescents (132 male participants; ages 15-17; 118 with ADHD). Parents provided ratings of adolescent routines, and adolescents provided ratings of coping behaviors and psychological adjustment in spring (May/June), summer (July/August), and fall (October/November) 2020. All models included the effects of adjustment at the prior timepoint as well as relevant covariates including adolescent race, ethnicity, sex, medication status, and family income. Adolescents with ADHD were at greater risk for experiencing increases in mental health symptoms and substance use throughout the pandemic, relative to adolescents without ADHD. The use of positive coping strategies and adolescent routines buffered against increases in substance use and mental health problems for adolescents with ADHD. These findings have important clinical and public policy relevance for parents, schools, and employers who may aim to prioritize keeping schedules as consistent as possible to promote healthy adjustment.