Interest in spatial ability has grown over the past few decades following the emergence of correlational evidence associating spatial aptitude with educational performance in the fields of science, technology, engineering, and mathematics. The research field at large and the anatomy education literature on this topic are mixed. In an attempt to generate consensus, a meta-analysis was performed to objectively summarize the effects of spatial ability on anatomy assessment performance across multiple studies and populations. Relevant studies published within the past 50 years (1969–2019) were retrieved from eight databases. Study eligibility screening was followed by a full-text review and data extraction. Use of the Mental Rotations Test (MRT) was required for study inclusion. Out of 2,450 screened records, 15 studies were meta-analyzed. Seventy-three percent of studies (11 of 15) were from the United States and Canada, and the majority (9 of 15) studied professional students. Across 15 studies and 1,245 participants, spatial ability was weakly associated with anatomy performance (rpooled = 0.240; CI at 95% = 0.09, 0.38; P = 0.002). Performance on spatial and relationship-based assessments (i.e., practical assessments and drawing tasks) was correlated with spatial ability, while performance on assessments utilizing non-spatial multiple-choice items was not correlated with spatial ability. A significant sex difference was also observed, wherein males outperformed females on spatial ability tasks. Given the role of spatial reasoning in learning anatomy, educators are encouraged to consider curriculum delivery modifications and a comprehensive assessment strategy so as not to disadvantage individuals with low spatial ability.