There is growing interest in the ways natural environments influence the development and progression of long-term health conditions. Vegetation and water bodies, also known as green and blue spaces, have the potential to affect health and behaviour through the provision of aesthetic spaces for relaxation, socialisation and physical activity. While research has previously assessed how green and blue spaces affect mental and physical wellbeing, little is known about the relationship between these exposures and health outcomes over time. This systematic review summarised the published evidence from longitudinal observational studies on the relationship between exposure to green and blue space with mental and physical health in adults. Included health outcomes were common mental health conditions, severe mental health conditions and noncommunicable diseases (NCDs). An online bibliographic search of six databases was completed in July 2020. After title, abstract and full-text screening, 44 eligible studies were included in the analysis. Depression, diabetes and obesity were the health conditions most frequently studied in longitudinal relationships. The majority of exposures included indicators of green space availability and urban green space accessibility. Few studies addressed the relationship between blue space and health. The narrative synthesis pointed towards mixed evidence of a protective relationship between exposure to green space and health. There was high heterogeneity in exposure measures and adjustment for confounding between studies. Future policy and research should seek a standardised approach towards measuring green and blue space exposures and employ theoretical grounds for confounder adjustment.