Palmer amaranth, an annual weed, and Verticillium dahliae, a fungal pathogen, can substantially reduce chile pepper yield. On the basis of the results of this study, we clarified implementation strategies for a potential management tactic for Palmer amaranth and V. dahliae in chile pepper: mustard seed meal (MSM). The objectives were to (1) determine MSM effects on Palmer amaranth seedbanks under different moisture levels, (2) measure glucosinolate degradation in soil hydrated to saturation and field capacity, and (3) determine the effects of decreasing moisture availability on MSM control of Palmer amaranth and V. dahliae. To address objective 1, seedbanks with and without MSM were hydrated to levels expected to both inhibit and promote germination (flooded, saturated, −0.03, −0.6 MPa, respectively). For objective 2, soil columns with MSM were held at different moisture levels and sampled over time. For objective 3, Palmer amaranth seeds were incubated with and without MSM, and with polyethylene glycol (PEG) solutions comprising a range of water potentials (0, −0.03, −0.6, −1.0, and −2.0 MPa). These PEG solutions were also used to hydrate MSM in agar plates with plugs of V. dahliae. All experiments were performed in growth chambers with temperatures and light conditions conducive to Palmer amaranth germination and V. dahliae mycelial growth. MSM-induced mortality in Palmer amaranth seedbanks was greater in soil at field capacity than in saturated soil and flooded soil; however, rates of glucosinolate degradation were greatest in saturated soil. Decreasing water availability progressively decreased the efficacy of MSM on Palmer amaranth because MSM was ineffective on nongerminated seeds. When incubated with PEG solutions with water potentials of 0, −0.03, and −0.6 MPa, MSM stopped growth of V. dahliae; however, MSM-induced control of V. dahliae was reduced by water potentials of −1.0 and −2.0 MPa. The results of this study indicate soils hydrated to field capacity maximize MSM-induced control of Palmer amaranth and V. dahliae.