Research examining physical activity interventions for mental disorders has grown exponentially in the past decade. At this critical juncture, there is a need to synthesize the best evidence to guide researchers, clinicians and people with lived experience. This meta-review aimed to systematically identify and comprehensively evaluate the current evidence about: a) the efficacy of physical activity interventions on mental, cognitive and physical outcomes for individuals with mental disorders; b) the potential neurobiological, psychosocial and behavioral mechanisms underlying the observed effects; and c) the barriers and facilitators for individuals to successfully engage in these interventions. Our systematic search identified 13 meta-analyses of high methodological quality (i.e., A Measurement Tool to Assess Systematic Reviews, AMSTAR score ≥8) assessing outcomes of physical activity as an adjunctive treatment, which included 256 randomized clinical trials (RCTs) and 12,233 individuals. Large effect sizes were found for adjunctive physical activity interventions in improving attention in children and adolescents with attention-deficit/hyperactivity disorder (ADHD); reducing depressive symptoms in children, adolescents and adults with depressive disorders; and reducing body mass index in adults with schizophrenia. Moderate effect sizes were found for reductions of hyperactivity, impulsivity and anxiety, and improvements of executive and social functioning in children and adolescents with ADHD; reduction of anxiety symptoms in adults with anxiety disorders; improved physical and psychological quality of life and cardiovascular fitness in adults with depressive disorders; improved daily living skills, overall quality of life and cardiorespiratory fitness in adults with schizophrenia; reduction of depressive symptoms in older people with depressive disorders; and improvements in cognition and functional mobility in older people with dementia. There is, to date, no meta-analytic evidence for physical activity as a first-line treatment for people with a mental disorder. Five meta-analyses, including 89 RCTs and 4,575 individuals, investigated potential underlying mechanisms. There is a very preliminary evidence for an effect of physical activity on circulating levels of kynurenine, growth hormone, tumor necrosis factor-alpha and brain-derived neurotrophic factor in people with major depressive disorder. No meta-analytic evidence could be found for psychosocial or behavioral mechanisms. Based on 15 umbrella or systematic reviews, covering 432 studies and 48 guidelines, six implementation strategies, along with the most evidence-based behavioral change techniques to support them, were identified. Recommendations to support implementation research in this area were finally formulated.