Iron deficiency chlorosis (IDC) and soybean cyst nematode (SCN; Heterodera glycines) infestation are major factors that contribute to soybean (Glycine max Merr.) yield reduction in the Midwest. The IDC is often associated with soybean grown on high pH, calcareous soils. In addition, it was documented that SCN population density is higher in high pH soils. The objectives of this paper were to assess the proportion of within-field soybean yield and SCN variability that could be explained by soil pH, calcium carbonate equivalent (CCE), and a previously defined alkalinity stress index (ASI). Aerial images from 21 fields planted to SCN-resistant or susceptible soybean varieties were collected from 2001 through 2005 and used as a guide for soil and grain sampling. Ten to 16 sampling sites were selected on each field. Regression analyses within and across sites were used to study relationships between the measured variables. The SCN population density increased and yield decreased with increasing pH, CCE, and ASI across the fields. The percentage of yield variability across fields explained by soil pH, CCE, ASI, and SCN was 13%, 15%, 18%, and 1%, respectively, for resistant soybean varieties and 37%, 24%, 39%, and 10%, respectively, for susceptible varieties. The yield reduction due to high pH, CCE, and ASI was greater for SCN-susceptible varieties in field areas heavily infested with SCN.