In theory, adaptive divergence can increase intrinsic post-zygotic reproductive isolation (RI), either directly via selection on loci associated with RI, or indirectly via linkage of incompatibility loci with loci under selection. To test this hypothesis, we measured RI at five intrinsic post-zygotic reproductive barriers between 18 taxa from the genera Cakile and Erucaria (Brassicaceae). Using a comparative framework, we tested whether the magnitude of RI was associated with genetic distance, geographic distance, ecological divergence, and parental mating system. Early stages of post-zygotic RI related to F1 viability (i.e., initial seed set) tended to be stronger than later stages related to F1 fecundity (i.e., flower number, fruit number). Mating system significantly influenced early stages of RI, such that RI was lowest when the mother was selfing and father was outcrossing, consistent with an imbalance between sink strength and resistance to provisioning. We found little evidence that adaptive divergence accelerates the evolution of intrinsic post-zygotic RI, consistent with non-ecological model of evolution that predicts the non-linear accumulation of RI and RI asymmetry with time (i.e., genetic distance), irrespective of adaptive divergence. Thus, while certain aspects of ecological divergence do not appear to have contributed strongly to the evolution of RI in this system, divergence in mating system actually reduced RI, suggesting that mating-system evolution may play a significant role in speciation dynamics.