The adoption of cover crop production systems is lagging in the mid-southern USA due to concerns over yield stability and on-farm profitability. This research was conducted to determine if the inclusion of a cover crop in conservation tillage systems improves yield, profitability, and water use efficiency. The effects of replacing subsoiling with a cereal rye (Secale cereale L.) or tillage radish (Raphanus sativus L. var. longipinnatus) cover crop on soybean [Glycine max (L.) Merr.] grain yield, net returns above specified costs, and water use efficiency were evaluated in a conservation tillage system, i.e., surface residue = 30% at planting, on a Dubbs silt loam (Fine-silty, mixed, active, thermic Typic Hapludalfs) from 2016 to 2018 near Stoneville, MS. Relative to the conservation tillage system with subsoiling, the replacement of subsoiling with a tillage radish cover crop reduced soybean grain yield, net returns above specified costs, and water use efficiency by up to 41% (P = 0.0266). Conversely, the replacement of subsoiling with a cereal rye cover crop had no effect on soybean grain yield or water use efficiency but reduced net returns above specified costs by 28% (P = 0.0266). In the mid-southern USA, a cereal rye cover crop can maintain soybean grain yield and water use efficiency relative to the regional standard, but widespread adoption of this production system is unlikely due to reduced profitability associated with additional seed and planting costs.