Domestication is an evolutionary process with an impact on plant reproduction. Many domesticated plants are self-compatible (i.e., they lack mechanisms to reject their own pollen), but few domesticated plants are fully or partially self-incompatible. We used the husk tomato, Physalis philadelphica, as a study model to investigate changes in the reproductive strategy of an annual partially self-incompatible plant during the process of domestication. Wild and cultivated populations of this species coexist in close proximity. These different populations present a high level of morphological and genetic variation associated with different degrees of domestication. We hypothesized that artificial selection favors self-compatibility in cultivated plants through changes in their reproductive strategy and some reproductive parameters associated with domestication. To test this hypothesis, we characterized the floral morphology and some reproductive parameters of weedy plants (wild plants), landraces (semi-domesticated plant), and commercial plants (domesticated plants). We conducted an artificial crossing experiment, germinated the seeds, and recorded seedling growth. Commercial plants had the largest flowers and the highest number of ovules. Yet, they did not differ in other reproductive parameters (e.g., herkogamy, size of pollen grains, stigmatic area, and pollen:ovule ratio) from landraces and weedy plants. Physalis philadelphica produced fruits by autonomous autogamy in the artificial crossing experiment. These fruits were the smallest and lightest fruits at all degrees of domestication; however, fruit set of autonomous autogamy was higher in weedy plants. In addition, fruit production was higher when weedy plants donated pollen to commercial plants. Although seeds produced by autonomous autogamy of weedy plants had a low germination percentage, their cotyledons and the embryonic foliage leaves appeared earlier than in landraces and commercial plants. In conclusion, the domestication syndrome in this plant was manifested as increments in flower size and ovule production. Contrary to expectations, there was higher fruit production by autonomous autogamy in weedy plants than in cultivated plants. It seems that artificial selection in P. philadelphica favors self-incompatibility in cultivated plants. Nonetheless, spontaneous self-pollination seems to be advantageous in weedy populations because they produced viable seeds from which cotyledons and the embryonic foliage leaves emerged earlier than in cultivated plants.