The invasive annual grass medusahead (Taeniatherum caput-medusae [L.] Nevski) degrades the ecosystem function throughout the sagebrush biome of the western United States. Currently, there are knowledge gaps regarding the fecundity of medusahead and the ability of defoliation treatments (grazing and mowing) to reduce annual seed production. Our research aimed to 1) determine if the timing of defoliation impacts the quantity of seeds produced, and 2) evaluate the impacts of defoliation on the viability of medusahead seeds produced. We used a randomized complete block design (n = 20) in a near-monoculture of medusahead located in southeast Oregon to assess the effectiveness of defoliation three times (November, March, and May) against a nondefoliated control from 2019 to 2022. Outcomes included gross seed production, germination statistics, and a linear regression to rapidly estimate seed production dependent on inflorescence length. We found no evidence that defoliation in November or March reduced seed production relative to the control in all years (P > 0.05). However, the May defoliation produced fewer seeds than the control in all 3 yr (P < 0.05). Defoliation of medusahead had no impact on the viability of seeds produced, with mean germination rates >80% in all treatment-year combinations. Findings did indicate that the number of seeds produced per tiller is strongly correlated with the length of inflorescence (R2 = 0.856), indicating that a generalized equation could be used to rapidly assess seed production in future works. The results of this study demonstrate that the effectiveness of defoliation is temporally limited and that the most effective treatments may still fail to reduce seed production by a meaningful degree. These findings indicate that defoliation treatments may be most effective included as a part of multifaceted, ecologically based treatments to effectively manage medusahead in the sagebrush biome.