The contribution of epistasis to 15 morphological traits differentiating two annual sunflowers (Helianthus annuus and H. debilis ssp. cucumerifolius) and to hybrid pollen sterility was estimated in a first generation backcross (BC1) mapping population. Analysis of digenic interactions among quantitative trait loci (QTLs) with significant main effects revealed significant interaction effects for six of the 15 morphological traits and for pollen sterility. Likewise, a genome-wide scan of all possible two-locus combinations detected additional significant interactions for three of the traits with significant epistasis in the original analysis: stem pigmentation, phyllary pubescence, and pollen viability. However, these were the only traits of the 16 examined in which detected interactions explained more than 5% of phenotypic variance. The implications of these findings for adaptive evolution and for the introgression of advantageous morphological QTLs across a natural hybrid zone between these taxa are discussed.