Containerized crop production faces increasing sustainability challenges with both soilless substrate and water use. To facilitate use of sustainable practices, we evaluated plant health impacts of two substrates, bark and wood fiber, which we contrasted with peat, a substrate that is slower to renew; this was overlaid with an analysis of the effects of water-saving–targeted irrigation reductions, compared with typical well-watered conditions. Health impacts were evaluated in two crops, considering both physiological and disease impacts for tomato with and without Phytophthora capsici, and chrysanthemum with and without Phytopythium helicoides. Substrate type was a strong determinant of plant health, wherein crops grown in a HydraFiber-peat mix (“fiber”) performed worse than those in bark and peat, with up to a 50% and 45% reduction in shoot biomass in tomato and chrysanthemum, respectively (P < 0.001). Tomato decline incidence from P. capsici was 3–6 times higher in fiber than other substrates, and fiber was the only substrate where the effect of P. capsici enhanced decline and rot development compared with noninoculated plants (P < 0.05). In bark, reduced irrigation consistently inhibited tomato and chrysanthemum growth and shoot water content (typically P < 0.001). In peat, whereas tomato growth was inhibited under reduced irrigation (P = 0.012–0.013), chrysanthemum growth was often unaffected. Growth in fiber was uniformly poor regardless of irrigation regime for both crops, and an irrigation treatment effect was not typically apparent. Reduced irrigation enhanced pathogen effects in fiber and peat for tomato and fiber and bark for chrysanthemum (P < 0.05). This is perhaps the first study to evaluate HydraFiber interactions with disease and reduced irrigation and suggests that this product consistently incurs costs to crop productivity. However, the peat-replacing bark substrate has strong potential to optimize plant growth physiologically and via disease suppression and can be used under reduced irrigation without compromising economic productivity of the system.