This study reports QTL mapping for seed yield and its components in safflower genome under drought stress. The F3 families derived from the cross Mex.22-191 (tolerant) × IL.111 (sensitive) were evaluated for agronomic traits in safflower. Drought tolerance was evaluated during 10% of the flowering stage. To identify QTLs underlying tolerance to drought, mapping quantitative trait loci (QTLs) was carried out by composite interval mapping function. A genetic linkage map (LG) assembled from SSR and ISSR markers, was mapped. A total of 145 DNA bands (SSR and ISSR markers) coalesced into 24 LGs which summed to 646 cM in the total map length. This analysis resulted in the identification of 18 QTLs related to seed yield and its components. Based on findings in this study, four major QTLs and three linkage groups (2, 4 and 6) played a crucial role in drought tolerance of safflower. The present linkage map may give a useful framework for mapping agronomic traits in safflower and the framework maps of C. tinctorius can serve as a foundation for future map integration, comparative genomics, QTL analysis and marker assisted breeding for drought tolerance.