Sesame (Sesamum indicum L.) is a market crop of small-scale farmers, particularly women, in the Sahel. Guidelines for soil fertility management may help to boost the productivity and profitability of sesame production. Research was conducted in 2016 and 2017 at Maradi and Magaria in Niger to determine nutrient response functions for sesame as a sole crop and intercropped with pearl millet (Pennisetum glaucum L.). Sesame yield was doubled with high consistency across site-years with 30 kg P ha(-1) applied and the P response function was determined. Sesame yield was not increased with N and K application. Manure application increased sesame grain yield by 25% when no fertilizer was applied and by 6% with 15 kg P ha(-1). The estimated fertilizer P equivalent value of manure P was 1.72 kg kg(-1) for no fertilizer P, indicating that manure application increased crop uptake capacity for indigenous soil P through, for example, increased root growth. Intercropped sesame and pearl millet yields decreased by about 41% of sole crop yields on average but the land equivalent ratio was about 1.2 with intercropping compared with sole crop production. The economically optimal P application rate ranged from 14 to 34 kg P ha(-1) for sesame sole crop and from 0 to 15 kg P ha(-1) for the intercrop with pearl millet, with the ranges resulting from varying fertilizer P use costs relative to crop value. Fertilizer P use has high profit potential for sesame sole crops in the Sahel but less potential for sesame-millet intercrops.