Virtual and augmented reality have seen increasing employment for teaching within medical and health sciences programs. For disciplines such as physiology and anatomy, these technologies may disrupt the traditional modes of teaching and content delivery. The objective of this systematic review and meta-analysis is to evaluate the impact of virtual reality or augmented reality on knowledge acquisition for students studying pre-clinical physiology and anatomy. The protocol was submitted to Prospero and literature search undertaken in PubMed, Embase, ERIC, and other databases. Citations were reviewed and articles published in full assessing learning or knowledge acquisition in pre-clinical physiology and anatomy from virtual or augmented reality were included. Of the 919 records found, 52 eligible articles were reviewed in full-text, with eight studies meeting full eligibility requirements. There was no significant difference in knowledge scores from combining the eight studies (626 participants), with the pooled difference being a non-significant increase of 2.9 percentage points (95% CI[-2.9;8.6]). For the four studies comparing virtual reality to traditional teaching, the pooled treatment effect difference was 5.8 percentage points (95% CI[-4.1;15.7]). For the five studies comparing augmented reality to traditional teaching, the pooled treatment effect difference was 0.07 (95% CI[-7.0;7.2]). Upon review of the literature, it is apparent that educators could benefit from adopting assessment processes that evaluate three-dimensional spatial understanding as a priority in physiology and anatomy. The overall evidence suggests that although test performance is not significantly enhanced with either mode, both virtual and augmented reality are viable alternatives to traditional methods of education in health sciences and medical courses.