Human-mediated selection can strongly influence the evolutionary response of natural organisms within ecological timescales. But what traits allow for, or even facilitate, adaptation to the strong selection humans impose on natural systems? Using a combination of lab and greenhouse studies of 32 natural populations of the common agricultural weed, Ipomoea purpurea, we show that herbicide resistant populations self-fertilize more than susceptible populations. We likewise show that anther-stigma distance, a floral trait associated with self-fertilization in this species, exhibits a non-linear relationship with resistance such that the most and least resistant populations exhibit lower anther-stigma separation compared to populations with moderate levels of resistance. Overall, our results extend the general finding that plant mating can be impacted by human-mediated agents of selection to that of the extreme selection of the agricultural system. This work highlights the influence of human-mediated selection on rapid responses of natural populations that can lead to unexpected long-term evolutionary consequences.