Benzobicyclon is a new pro-herbicide being evaluated in the Midsouth United States as a post-flood weed control option in rice. Applications of benzobicyclon to flooded rice are necessary for efficacious herbicide activity, but why this is so remains unknown. Two greenhouse experiments were conducted to explore how herbicide placement (foliage only, flood water only, foliage and flood water simultaneously) and adjuvants (nonionic surfactant, crop oil concentrate, and methylated seed oil [MSO]) affect herbicide activity. The first experiment focused on importance of herbicide placement. Little to no herbicidal activity (<18% visual control) was observed on two- to four-leaf barnyardgrass, Amazon sprangletop, and benzobicyclon-susceptible weedy rice with benzobicyclon treatments applied to weed foliage only. In contrast, applications made only to the flood water accounted for >82% of the weed control and biomass reduction achieved when benzobicyclon was applied to flood water and foliage simultaneously. The second experiment concentrated on adjuvant type and benzobicyclon efficacy when applied to foliage and flood water simultaneously. At 28 days after treatment, benzobicyclon alone at 371 g ai ha−1 provided 29% and 67% control of three- to five-leaf barnyardgrass and Amazon sprangletop, respectively. The inclusion of any adjuvant significantly increased control, with MSO providing near-complete control of barnyardgrass and Amazon sprangletop. Furthermore, we used the physiochemical properties of benzobicyclon and benzobicyclon hydrolysate to derive theories to explain the complex activity of benzobicyclon observed in our study and in field trials. Benzobicyclon applications should contain an oil-based adjuvant and must be applied to flooded rice fields for optimal activity.