The repeated evolution of herbicide resistance in agriculture provides an unprecedented opportunity to understand how organisms rapidly respond to strong anthropogenic-driven selection pressure. In populations of the grass species Bromus tectorum L., resistance to multiple herbicides has been recently identified. To understand the evolutionary origins and spread of resistance, we investigated the resistance mechanisms in 49 B. tectorum populations to acetolactate synthase (ALS) inhibitors and photosystem II inhibitors, two widely used herbicide modes of action. We assessed the genetic diversity, structure, and relatedness in a subset of 21 populations. Resistance to ALS inhibitors was associated with multiple types of non-synonymous mutations in ALS, the target site gene. Mechanisms not related to the target site evolved and were common in the populations studied. Resistance to photosystem II inhibitors was confirmed in two populations and was conferred by non-synonymous mutations in the plastid gene psbA. Population genetics analyses showed low levels of genetic diversity, suggesting that local selection pressure processes have shaped the populations. We also found evidence of long-distance gene flow among distinct growing regions and cropping systems. The results suggest that both gene flow via pollen and/or seed dispersal, and multiple local and independent evolutionary events were involved in the spread of herbicide-resistant B. tectorum. Our results provide an empirical example of the rapid repeated evolution of a trait under strong anthropogenic selection and elucidate the evolutionary origins of herbicide resistance in a plant species of agricultural importance.