Precise knowledge of safflower (Carthamus tinctorius L.) nitrogen (N) dynamics is essential to optimize crop nutrition and minimize environmental impacts of fertilizers. Two-year field experiments were conducted to evaluate the influence of N rates (0, 100 and 200 kg ha−1) and genotype (hybrids vs. open pollinated variety) on N uptake, distribution, remobilization and use, and to quantify the relative contribution of different plant organs as N-providers to seed in dryland Mediterranean safflower. The rate of 100 kg N ha−1 was adequate to maximize N content at anthesis and N use efficiency. Early N uptake was a key physiological process that largely determined the N dynamics during the achene-filling period. Enhanced N content at anthesis improved N remobilization from vegetative parts to achenes, with capitulum vegetative components (including bracts) contributing to N remobilization, on average, more (69%) than leaf plus stems (31%). The N remobilization efficiency ranged between 56 and 63%. High early N accumulation (> 158 kg N ha−1) and low sink N (< 113 kg N ha−1) resulted in N losses from plants during the post-anthesis period. Nitrogen application had no influence on the N harvest index or the efficiency of biomass production. Selection for improved N utilization efficiency would theoretically penalize achene protein content due to the negative correlation between these parameters. Safflower produced up to 32 kg achene yield per unit of N taken up. The inclusion of safflower in the rotation system of winter cereals in semiarid Mediterranean environments, apart from the diversification of cropping systems might keep the overall N utilization efficiency unchanged.