To investigate patterns of gender-based performance gaps, we conducted a meta-analysis of published studies and unpublished data collected across 169 undergraduate biology and chemistry courses. While we did not detect an overall gender gap in performance, heterogeneity analyses suggested further analysis was warranted, so we investigated whether attributes of the learning environment impacted performance disparities on the basis of gender. Several factors moderated performance differences, including class size, assessment type, and pedagogy. Specifically, we found evidence that larger classes, reliance on exams, and undisrupted, traditional lecture were associated with lower grades for women. We discuss our results in the context of natural science courses and conclude by making recommendations for instructional practices and future research to promote gender equity.