The value of whole cottonseed and cottonseed products has increased as demand has grown from the dairy and food related industries. Although cottonseed composition has previously been documented to be affected by variety, planting date, and irrigation, interactions between varieties and irrigation regimes have not been adequately described. Six different varieties were planted on two planting dates and grown under irrigated or dryland conditions to document how varieties interacted with irrigation regimes to impact various seed composition traits. Variety was a major source of variation for all the seed composition traits quantified. Individual seed mass variation among varieties could explain some of the seed composition variation observed, particularly for protein. For many of these seed composition traits, variety also interacted statistically with irrigation regimes to impact trait expression. Most seed composition traits of the varieties responded in the same direction to irrigation, but there was sufficient variety variation in the response that significant interactions were produced. ‘ST 5599BR’ often exhibited a different irrigation response compared to the other varieties, particularly for the different fatty acid components. These results indicate that a pairing of varieties and management practices could be utilized to help achieve desired seed composition traits. Although lint production is the primary economic incentive for cotton producers, improved cottonseed composition offers an important, consistent, and reliable secondary revenue stream for producers.