Human driven changes in the Earth's atmospheric composition are likely to alter plant disease in the future. We evaluated the effects of elevated carbon dioxide (CO2) and ozone (O3) on three economically important soybean diseases (downy mildew, Septoria brown spot and sudden death syndrome-SDS) under natural field conditions at the soybean free air concentration enrichment (SoyFACE) facility. Disease incidence and/or severity were quantified from 2005 to 2007 using visual surveys and digital image analysis, and changes were related to microclimatic variability and to structural and chemical changes in soybean host plants. Changes in atmospheric composition altered disease expression, but responses of the three pathosystems varied considerably. Elevated CO2 alone or in combination with O3 significantly reduced downy mildew disease severity (measured as area under the disease progress curve-AUDPC) by 39–66% across the 3 years of the study. In contrast, elevated CO2 alone or in combination with O3 significantly increased brown spot severity in all 3 years, but the increase was small in magnitude. When brown spot severity was assessed in relation to differences in canopy height induced by the atmospheric treatments, disease severity increased under combined elevated CO2 and O3 treatment in only one of the 3 years. The atmospheric treatments had no effect on the incidence of SDS or brown spot throughout the study. Higher precipitation during the 2006 growing season was associated with increased AUDPC severity across all treatments by 2.7 and 1.4 times for downy mildew and brown spot, respectively, compared with drought conditions in 2005. In the 2 years with similar precipitation, the higher daily temperatures in the late spring of 2007 were associated with increased severity of downy mildew and brown spot. Elevated CO2 and O3 induced changes in the soybean canopy density and leaf age likely contributed to the disease expression modifications.