Corn (Zea mays L.) and soybeans (Glycine max (L.) Merr.) are major annual crops grown in yearly rotation in Iowa. The economic returns of both crops with different tillage systems and crop rotations are highly influenced by regional soil and climate conditions. This study was conducted at seven locations in Iowa from 2003 to 2013 with the objectives to: (i) investigate seasonal variability in corn and soybean yields as affected by tillage and crop rotation, (ii) identify appropriate tillage system for each crop rotation and location, and (iii) evaluate the magnitude of crop rotation effect on the yields and economic returns of both corn and soybean.