Weedy rice refers to the unwanted plants of the genus Oryza that have some undesirable agronomic traits and pose a major threat to sustainable rice production worldwide. Widespread adoption of direct seeded rice and hybridization or gene flow between cultivated rice and their wild relatives has resulted in the creation and dissemination of weedy rice. Currently, weedy rice (Oryza sativa f. spontanea) has become one of the most common weeds infesting rice fields worldwide. In this paper, we review the biology, physiology, evolution, and genetic features of weedy rice. We also discuss the major obstacles in weedy rice management, including high diversity of weedy rice, ecological impacts of gene flow on weedy rice, changing climate, and weedy rice management. We then present a framework for the sustainable management and utilization of weedy rice. Our main emphasis is to explore the reservoir of natural variations in weedy germplasm and to utilize them for crop improvement. This review outlines some of the latest biotechnological tools to dissect the genetic backgrounds of several favorable traits of weedy rice that may prove beneficial for breeding and evolutionary studies on cultivated rice. We suggest that by merging the disciplines of genomics, breeding, and weed management, we can achieve the goal of sustainable rice production.