Experiment was conducted during kharif season of 2013 and 2014 under rainfed conditions using sesame variety RT 346 in sandy loam soil at Regional Research Station (Punjab Agricultural University) Ballowal Saunkhri district SBS Nagar (Punjab). The aim of the study was to assess the effect of different levels of N, P and K on seed yield, nutrient uptake and agronomic efficiencies in sesame. The experiment was laid out in randomized block design with 6 treatments N: P2O5: K2O viz, Control, 35: 0: 0 (basal dose), 35: 0: 0 (basal dose) + 10 ton FYM/ha, 70: 0: 0 (2 N splits), 70: 40: 0 (2 N splits), 70: 40: 15 (2 N splits). Among the different treatments, application of N: P2O5: K2O as 70: 40: 0 with nitrogen in two splits recorded the maximum values for growth parameters viz., plant height, number of branches per plant and yield attributes viz., number of capsules per plant and number of seeds per capsule, and this treatment was at par with application of N: P2O5: K2O applied as 70: 0: 0 treatment (2 N splits) and 35: 0: 0 + 10 ton FYM/ha treatment. Highest average seed yield of 852 kg/ha was recorded with treatment 70: 40: 0 with nitrogen in two splits which was 44% higher over the control treatment. The nitrogen, phosphorus and potassium uptake was also highest in the treatment N: P2O5: K2O as 70: 40: 0 followed by 70: 0: 0 and 35: 0: 0 + 10t/ha FYM, which was significantly higher over the control treatment. The net return (` 42, 545) and B: C ratio (3.34) was also highest in the treatment 70: 40: 0 as compared to the other treatment.