Most plants are capable of photosynthesis, but not all plants photosynthesize in the same way. There are at least two alternative modes of photosynthesis in flowering plants, one of which – Crassulacean acid metabolism, or CAM – is found in about 8% of angiosperms and has evolved at least 80 times independently. CAM plants open their stomata for gas exchange at night, when transpiration is relatively lower than during the day, and store incoming CO2 as malic acid. In the daytime, the malic acid is decarboxylated and surrounds Rubisco behind closed stomata, essentially concentrating CO2 in the leaves. Moreover, there is great variation in the degree to which a plant uses CAM. Some species, called “strong” or constitutive CAM plants, obtain nearly all their CO2 via CAM, while other species use CAM only a fraction of the time. To assist with storage of malic acid, it is thought that strong CAM plants require large, densely packed cells in the leaves. However, our understanding of how anatomy evolves relative to the biochemical pathway of CAM remains unclear. Preliminary data in the Agavoideae (Asparagaceae), which includes iconic desert species like agaves and yucca, showed three independent origins of CAM in the subfamily. Furthermore, evidence suggested that large cells evolved before CAM, perhaps to aid with water storage in arid habitats. Here we broadened sampling and measured leaf anatomical traits in ~50 species in the Agavoideae to investigate leaf anatomical evolution across the subfamily and within the three CAM lineages. We further examined the association between historical climate, CAM, and anatomical trait evolution across the subfamily. In contrast to early data, we find that independent CAM lineages in the Agavoideae possess very different anatomical traits, suggesting they have each independently evolved or elaborated on CAM-like leaf anatomy.