Background Running is a popular activity practiced worldwide. It is important to understand how running affects joint health to provide recommendations to sports medicine practitioners and runners. Objective Our aim was to summarize the influence of running on lower limb cartilage morphology and composition using quantitative magnetic resonance imaging (MRI). Methods Prospective repeated-measures studies evaluating cartilage using MRI before and after running were included. Data sources included Pubmed, Embase, CINAHL, SportDiscus, Web of Science, and Cochrane Central Registry of Controlled Trials. Qualitative analyses considered the number and methodological quality ratings of studies based on the QualSyst tool, and recommendations were based on the strength of evidence (strong, moderate, limited, or very limited). Quantitative analysis involved meta-analyses, for which effect sizes were calculated as Hedge’s g standardized mean differences. Results We included 43 articles, assessing seven outcomes (lesions, volume, thickness, glycosaminoglycan content, and T1ρ, T2, and T2* relaxation times). Nineteen articles were rated as high quality, 24 were rated as moderate quality, and none were rated as low quality. Qualitative analyses suggest that running may cause an immediate reduction in knee cartilage volume, thickness, as well as T1ρ and T2 relaxation times immediately; however, these changes did not persist. Meta-analyses revealed a small and moderate decrease immediately following a single running bout in T2 relaxation time in the medial femur and tibia, respectively. Qualitative analyses indicated that the influence of repeated exposure to running on cartilage morphology and composition was limited. Despite conflicting evidence regarding pre-existing knee cartilage lesions, moderate evidence suggests that running does not lead to the formation of new lesions. Repeated running exposure did not cause changes to foot and ankle cartilage thickness or composition. Conclusions Changes to lower limb cartilage following running are transient. Immediate changes to cartilage morphology and composition, which likely reflect natural fluid dynamics, do not persist and were generally not significant when pooled statistically. Results suggest that cartilage recovers well from a single running bout and adapts to repeated exposure. Given that moderate evidence indicates that running does not lead to new lesions, future trials should focus on clinical populations, such as those with osteoarthritis.