Cotton is picked manually in Fars Province, Iran. It is not only a slow, labor-intensive operation, but extremely tedious, hard work. Due to scarcity of labor at harvesting time, mechanization of cotton harvesting is of vital importance. Therefore, a field study was conducted to evaluate the interactive effects of harvesting directions (in the rows, cross, and oblique, or skew) and row spacing (24-, 36-, and 70-cm) on cotton stripper performance. Results showed that different harvesting directions and row spacing had a significant effect on seed cotton loss. Maximum seed cotton loss was observed in the row direction treatment and minimum loss occurred in the skew treatment. The findings revealed that maximum loss was obtained from row spacing of 70 cm. Overall, these results demonstrated that cotton grown in 36-cm rows and harvested in a skewed or oblique direction had a greater impact on the reduction of seed cotton losses and produced seed cotton yield higher than the 70-cm rows harvested in the rows direction.