As the effects of global climate change intensify, the interaction of biotic and abiotic stresses increasingly threatens agriculture. The secondary cell wall is a vanguard of resistance to these stresses. Fusarium thapsinum (Fusarium stalk rot) and Macrophomina phaseolina (charcoal rot) cause internal damage to the stalks of the drought tolerant C4 grass, sorghum (Sorghum bicolor (L.) Moench), resulting in reduced transpiration, reduced photosynthesis, and lodging, severely reducing yields. Drought magnifies these losses. The interaction of water limitation with F. thapsinum or M. phaseolina infection was investigated using two monolignol biosynthetic mutants in sorghum, bmr6 and bmr12. bmr12 inoculated with each of these pathogens had significantly reduced lesion sizes under water limitation compared to adequate watering and had increased levels of salicylic acid under both conditions, suggesting that drought may prime induction of pathogen resistance. Coexpression analysis under disease and drought reveals a wealth of interacting pathways including cell wall remodeling, phytohormones, spliceosome, proteasome, and amino acid and central metabolism. Coexpression modules are associated with pathogens and soil moisture and interact with day length and plant size, highlighting the tradeoff between growth and defense and its interaction with secondary cell wall biosynthesis and offering promising new engineering targets for plants robust to these interacting stresses.