Mali is among Africa's three biggest cotton (Gossypium hirsutum L.)‐producing countries, and cotton growing is the principal driving force behind Mali's agricultural sector. Cotton production is rainfed on small‐scale family farms as a commercial crop alongside staple crops grown for subsistence. Cultivar choice, planting date, and planting density are critical elements for seed cotton yield that should be optimized. This study aimed to understand the interactions between planting dates and planting densities for the optimal production of four cotton cultivars in Mali. Two trials were set up in two seasons at the Finkolo and N'Tarla research stations. A split‐plot design with four replications was used, with planting dates (early and delayed by 3 weeks) as the main plots and planting density (41,666; 83,333; and 166,666 plants/ha) and cultivar (Malian NTA MS334, Togolese STAM 129A, Australian SIOKRA L23, and Brazilian BRS 293) as the subplots. In 2021, seed cotton yield was 1263 kg/ha for early planting versus 361 kg/ha for late planting. Medium and high planting densities produced the same yield level, higher than the low planting density. Regardless of the planting density, early plantings' average capsular weight and seed index were higher than those of late plantings. The African cultivars (STAM 129A and Malian cultivar NTA MS334) were the most productive. Due to significant interactions on fiber percentage and to optimize cotton yields in Mali, planting should be early, with planting densities higher than 41,666 plants/ha, and either of the African cultivars tested should be used.