The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity. Significance Plants that provide food and housing to animals in return for defense against enemies are classic examples of mutualistic partnerships in nature. Here, we show that the evolution of such plant–animal mutualisms also can lead to a trajectory of accelerated accumulation of plant species in the lineages that participate in these cooperative interactions. We found that the evolution of plant organs (extrafloral nectaries) that facilitate mutualisms with animal defenders was repeatedly followed by increased rates of diversification across distantly related plant lineages. These results suggest that by enabling ecological interactions with animals, the convergent evolution of relatively simple glands changed the course of plant evolution toward greater protection from pests and accelerated the generation of biodiversity.