Much recent research has focused on the relation between spatial skills and mathematical skills, which has resulted in widely reported links between these two skill sets. However, the magnitude of this relation is unclear. Furthermore, it is of interest whether this relation differs in size based on key demographic variables, such as gender and grade-level, and the extent to which this relation can be accounted for by shared domain-general reasoning skills across the two domains. Here we present the results of two meta-analytic studies synthesizing the findings from 45 articles to identify the magnitude of the relation, as well as potential moderators and mediators. The first meta-analysis employed correlated and hierarchical effects meta-regression models to examine the magnitude of the relation between spatial and mathematical skills, and to understand the effect of gender and grade-level on the association. The second meta-analysis employed meta-analytic structural equation modeling to determine how domain-general reasoning skills, specifically fluid reasoning and verbal skills, influence the relationship. Results revealed a positive moderate association between spatial and mathematical skills (r =.36, robust standard error = 0.035, τ2 = 0.039). However, no significant effect of gender or grade-level on the association was found. Additionally, we found that fluid reasoning and verbal skills mediated the relationship between spatial skills and mathematical skills, but a unique relation between the spatial and mathematical skills remained. Implications of these findings include advancing our understanding for how to leverage and bolster students’ spatial skills as a mechanism for improving mathematical outcomes.