Objective: Although the COVID-19 pandemic has affected mental health, understanding who has been affected most and why is incomplete. We sought to understand changes in mental health in the context of transmission numbers and pandemic (social) restrictions and whether changes in mental health varied among population groups. Methods: We analyzed data from 92 062 people (aged ≥16 years and able to read Dutch) who participated in the Corona Behavioral Unit cohort study at the National Institute for Public Health and the Environment, the Netherlands, from April 17, 2020, through January 25, 2022. Participants self-reported mental well-being through multiple rounds of surveys. We used a multivariable linear mixed-effects model to analyze loneliness, general mental health, and life satisfaction. Results: As strictness of pandemic prevention measures and social restrictions increased, people’s feelings of loneliness increased and mental health and life satisfaction decreased. As restrictions were relaxed, loneliness decreased and general mental health improved. Younger people (aged 16-24 y) versus older people (aged ≥40 y), people with low (vs high) education levels, and people living alone (vs living together) were more likely to have negative well-being outcomes. We observed that trajectories over time differed considerably only by age, with participants aged 16-24 years affected substantially more than participants aged ≥40 years by pandemic social restrictions. These patterns were consistent across multiple waves of SARS-CoV-2 infection. Conclusions: Our findings suggest that the social restrictions imposed by the Dutch government during the study period were associated with reduced mental well-being, especially among younger people. However, people appeared resilient as they recovered during periods when restrictions were relaxed. Monitoring and supporting well-being, in particular to reduce loneliness, may help younger people during periods of intense social restrictions.