The columnar cactus Stenocereus stellatus is used in Central Mexico for its edible fruits which are harvested in wild, managed in situ and cultivated populations. Management in situ of wild populations is conducted by selectively sparing and enhancing the abundance of plants with desirable phenotypes when fields are cleared for agricultural use. Cultivation of desirable phenotypes is carried out by vegetative propagation in homegardens. Effects of human management on morphological and genetic variation of S. stellatus were analyzed by comparing morphological diversity indices (MD, based on Simpson’s index) and expected (He) heterozygosity indices from allozyme analysis, in wild, managed in situ, and cultivated populations from La Mixteca and the Tehuacan Valley regions. Morphological diversity was similar among regions, but populations from the wetter La Mixteca region averaged higher genetic variation (He = 0.279) than populations from Tehuacan (He = 0.265). On average, populations manipulated by people had higher levels of variation (MD = 0.479 ± 0.012, He = 0.289 in cultivated populations; MD = 0.461 ± 0.014, He = 0.270 in managed in situ populations) than wild populations (MD = 0.408 ± 0.017, He = 0.253), which is apparently due to a continual introduction and replacement of plant materials in the manipulated populations. The results illustrate that human management may not only maintain but also increase both morphological and genetic diversity of manipulated plant populations in relation to that existing in the wild. Managed in situ and cultivated populations of S. stellatus are important reservoirs of variation, and are crucial for the general maintenance of diversity in wild populations. These populations may play a principal role in designing strategies for the conservation of variation of this cactus.