Sulfur deficiency in Indiana soybean [Glycine max (L.) Merr.] production may be an underrated yield-limiting factor. As environmental standards for air quality have increased, the amount of atmospheric sulfate deposited on Indiana soils has fallen dramatically. As soybean yields continue to rise and remove more sulfur from fields with each harvest, the need for applications of sulfur-containing fertilizers increases. The likelihood of seeing a soybean yield response to sulfur applications is greatly influenced by climate and site factors associated with soils. Applications of ammonium sulfate (AMS) were made at 65 sites across Indiana in 2018 to measure the yield response to sulfur fertilization. Seven of the sites had multiple replications of the control and sulfur treatments and at the other 58, treatments were unreplicated. AMS was applied at 100 pounds per acre in strips, equivalent to 24 pounds of sulfur per acre. In addition to yield, several variables were measured, including: planting and harvest dates, previous crop, irrigation, precipitation, solar radiation, temperature, tillage, seeding rate, row width, soil organic matter, and cation exchange capacity. Yield response to AMS at sites with replicated treatments averaged 2.7 bushel per acre. Results from all 65 locations yielded an average of 1.4 bushel per acre increase from applications of 100 pounds of AMS per acre. It costs $5.16 on average to apply 100 pounds of AMS. The value of the yield increase found through this study is three to five-fold the cost of application. Sulfur is a profitable consideration for many Indiana soybean farmers.