Land application of co-produced waters from coalbed natural gas (CBNG) wells is one management option used in the Powder River Basin (PRB) of Wyoming and Montana. Unfortunately, the co-produced CBNG waters may be saline and/or sodic. The objective of this study was to examine the effects of irrigation with CBNG waters on soils and plants in the PRB. Soil properties and vegetation responses resulting from 1 to 4 yr of saline-sodic water (electrical conductivity [EC], 1.6–4.8 dS m−1; sodium adsorption ratio [SAR], 17–57 mmol1/2 L−1/2) applications were studied during 2003 and 2004 field seasons on sites (Ustic Torriorthent, Haplocambid, Haplargid, and Paleargid) representing native range grasslands, seeded grass hayfields, and alfalfa hayfields. Parameters measured from each irrigated site were compared directly with representative non-irrigated sites. Soil chemical and physical parameters, including pH, EC, SAR, exchangeable sodium percent, texture, bulk density, infiltration, and Darcy flux rates, were measured at various depth intervals to 120 cm. Multiple-year applications of saline-sodic water produced consistent trends of increased soil EC and SAR values to depths of 30 cm, reduced surface infiltration rates, and lowered Darcy flux rates to 120 cm. Significant differences (p ≤ 0.05) were determined between irrigated and non-irrigated areas for EC, SAR, infiltration rates, and Darcy flux (p ≤ 0.10) at most sites. Saline-sodic CBNG water applications significantly increased native perennial grass biomass production and cover on irrigated as compared with non-irrigated sites; however, overall species evenness decreased. Biological effects were variable and complex, reflecting site-specific conditions and water and soil management strategies.