<b><i>Introduction:</i></b> People living with chronic diseases are at an increased risk of anxiety and depression, which are associated with poorer medical and psychosocial outcomes. Many studies have examined the trajectories of depression and anxiety in people with specific diseases, including the predictors of these trajectories. This is valuable for understanding the process of adjustment to diseases and informing treatment planning. However, no review has yet synthesised this information across chronic diseases. <b><i>Methods:</i></b> Electronic databases were searched for studies reporting trajectories of depression or anxiety in chronic disease samples. Data extracted included sample characteristics, results from trajectory analyses, and predictors of trajectories. Meta-analysis of the overall pooled prevalence of depression and anxiety trajectories was conducted, and qualitative synthesis of disease severity predictors was undertaken. <b><i>Results:</i></b> Following search and screening, 67 studies were included (<i>N</i> = 61,201 participants). Most participants followed a stable nonclinical trajectory for depression (69.0% [95% CI: 65.6, 72.2]) and anxiety (73.4% [95% CI: 66.3, 79.5]). Smaller but meaningful subsamples followed a trajectory of depression and anxiety symptoms consistently in the clinical range (11.8% [95% CI: 9.2, 14.8] and 13.7% [95% CI: 9.3, 19.7], respectively). Several clinical and methodological moderators emerged, and qualitative synthesis suggested that few aspects of disease severity were associated with participants’ trajectories. <b><i>Conclusion:</i></b> Most people with chronic disease follow a trajectory of distress that is low and stable, suggesting that most people psychologically adjust to living with chronic disease. Evidence also suggests that the nature and severity of the disease are not meaningful predictors of psychological distress.