The present study aimed to investigate the trajectories of adjustment disorder (AD) symptoms and well-being over 20 months of the COVID-19 pandemic in Austria and Croatia. Further objectives of this study were to examine whether sociodemographic characteristics and the symptoms of anxiety and depression could predict these trajectories. As part of the pan-European ESTSS ADJUST study, N = 1144 individuals were recruited using convenience sampling and assessed four times between June 2020 and January 2022 through an online survey. Latent growth curve modelling was applied to estimate the trajectories of AD symptoms and well-being. Over time, the prevalence of probable AD varied between 9.8% and 15.1%. The symptoms of AD tended to increase, whereas well-being tended to decrease. According to the majority of the models tested, women, participants from Austria and those with lower income had higher initial AD symptoms, whereas older participants and those from Croatia had higher initial well-being. In all models and at all timepoints, anxiety and depression significantly predicted AD and well-being scores. Overall, our study points to several predictors of AD and well-being and indicates high variability in people’s reactions to the pandemic. Psychosocial support for the general population is needed during pandemics and similar crises, with a special focus on vulnerable groups.