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Sorghum (Sorghum bicolor (L) Moench) is a staple food in Africa, South Asia and Central America. In Cameroon, it is the main food of the population of the Sudano-Sahelian zone. Its production could decline by up to 20% by the middle of the century, due to climatic disturbances. This climatic disturbance in Cameroon has led to several consequences among which, low crop yields. The comparative effect of the biological fixation of nitrogen and chemical fertilizer on the optimization of yield of two varieties of Sorghum, was conducted from July to October at IRAD (Institute of Agricultural Research for Development) station of Foumbot. The experimental design was a complete randomized block with two factors: varieties of sorghum (V1: S35 and V2: BIOGLOR) and treatments (T0: Control, T1: 20-10-10 and T2: Sorghum / NITU beans). The collar diameter, the number of leaves and plant height were evaluated each week and yield in the end of the cropping season. As a result, treatment T1 induced very significantly (P ˂ .01) growth (shoot length, leaf and collar diameter). T1 (V1: 1.30 ± 0.11 t.ha-1, V2: 2.01 ± 0.07 t.ha-1) and T2 (V1: 1.12 ± 0.02 t.ha-1, V2: 2.15 ± 0.03 t.ha-1) showed statistically equal yields, and significantly different from T0 (V1: 0.50 ± 0.06 t.ha-1, V2: 0.55 ± 0.05 t.ha-1). The BIOGLOR variety had the highest yield (1.57 ± 0.57 t.ha-1) compared to the S35 variety (0.97 ± 0.19 t.ha-1). The treatment T2 is the recommended fertilizer system because of the higher grain yield of sorghum and its ability to protect the environment.