A 2-year field experiment was conducted to evaluate the effect of N sources [Ammonium Nitrate (AN), Ammonium Sulfate (AS), Sulfur Coated Urea (SCU), and Urea (U)] and split application ((1/4, 3/4, 0), (1/3, 1/3, 1/3), (1/2, 1/2, 0), and (1/3, 2/3, 0)) on weed growth, safflower (Carthamus tinctorius L. ) yield, and N Use Efficiency (NUE), using a split split-plot design with three replications, at the Experimental Research Station of Shiraz University, in 2015 and 2016. In weedy plots, applying AN-fertilizer in a split pattern of 1/2, 1/2, 0 (applying half of the N at sowing time and the rest at stem elongation) increased weed infestation. This treatment enhanced total weed N Uptake Efficiency (NUpE) up to 5% compared to U-fertilizer and similar split pattern. In weed free plots, the highest seed and oil yields (3303. 52 and 753. 09 kg ha-1, respectively) were achieved by AN-and U-fertilizers in a split pattern of 1/2, 1/2, 0. Applying AN fertilizer and split patterns of 1/3, 2/3, 0 (one third of N at sowing and two thirds at stem elongation) and 1/4, 3/4, 0 (one quarter of N at sowing and three quarters at stem elongation) maximized safflower NUpE (0. 78 kg kg-1). Applying U fertilizer and split pattern of 1/2, 1/2, 0 increased safflower ability to compete vs. weeds up to 20% compared to AN-fertilizer. Overall, in order to improve safflower yield and NUE and control weed, applying U-fertilizer and split application of 1/3, 2/3, 0 or 1/4, 3/4, 0 can be suggested as a component of integrated weed management programs.