Effective weed seedbank management requires mechanistic understanding of ecological determinants of seed persistence in the soil seedbank. Chemical and physical defense of common lambsquarters, field pennycress, giant foxtail, kochia, velvetleaf, and yellow foxtail seeds were quantified in relation to short- and long-term seedbank persistence. Seed content of ortho-dihydroxyphenols (o-DHP), a class of putative seed defense compounds, varied more than threefold between the least protected species (common lambsquarters, 9.2 µg g seed−1) and the most protected species (kochia, 34.1 µg g seed−1). Seed o-DHP was inversely related (r = −0.77, P < 0.001) to seed half-life in the soil and to short-term seed persistence in burial assays (r = −0.82, P < 0.05). The relative importance of chemical seed protection in comparison to physical seed protection, as represented by the ratio of seed o-DHP concentration to seed coat thickness, decreased linearly with increasing short-term seed persistence (r = −0.96, P < 0.01) and nonlinearly with increasing long-term seed persistence in the soil seedbank (y = 0.16 + 0.21/(0.0432 + x), R2 = 0.99, P < 0.001). Mechanical damage to the seed coat, via piercing, slicing, or grinding treatments, increased short-term mortality during burial for all six species. Mortality of pierced seeds was negatively associated (r = −0.35, P < 0.05) with seed phenol concentration and positively associated with seed half-life (r = 0.42, P < 0.01) and seed coat thickness (r = 0.36, P < 0.05). Seed phenolics, as a class, supported the results for o-DHPs. Overall, these findings suggest a potential weakness, with respect to seedbank management, in the way weed seed defenses are constructed. Weed species with transient seedbanks appear to invest more in chemical defense than those species with highly persistent seedbanks. As a result, seeds in the latter category are relatively more dependent upon physical seed protection for persistence in the soil seedbank, and more vulnerable to management tactics that reduce the physical integrity of the weed seed coat.