The quantification of nutrient uptake and partitioning during crop cultivation, as well as nutrients removed at harvest, are essential information to optimize nutrient management. A 2‐yr field experiment was conducted in Botucatu, São Paulo State, southeastern Brazil, to examine the biomass accumulation and nutritional requirements and removal of two safflower (Carthamus tinctorius L.) genotypes cultivated in the fall‐winter season of a double‐cropping system. Seven plant samplings were performed during the growing season, and the material was divided into stems, leaves, and reproductive structures. Seed yield and nutrient removal were determined at harvest. Safflower genotypes had similar 2‐yr average biomass accumulations and seed yields. There were greater plant growth and nutrient uptake from stem elongation to seed filling, compared to the other growth stages. The maximum rates of nutrient uptake were observed near the flowering stage. On average, a maximum uptake of 169 kg N, 16 kg P, 178 kg K, 121 kg Ca, 16 kg Mg, 15 kg S, 130 g Cu, 3298 g Fe, 420 g Mn, and 351 g Zn per hectare were required to produce about 10,500 and 1,400 kg ha−1 of aboveground biomass and seeds, respectively. Relative to the maximum aboveground nutrient accumulation, seeds contained 28% of P, 24% of N, 22% of Zn, 16% of Cu, 11% of Mg, 10% of S, 6% of K, 5% of Mn, 4% of Ca, and 4% of Fe. These quantifications of biomass and nutrient accumulation and partitioning in each growth stage of fall‐winter safflower can be used as guidelines for fertilizer recommendations for this crop in double‐cropping systems.