Inoculating groundnut and cowpea with highly effective and competitive rhizobial strain improves nodulation. A field experiment was carried out at the experimental field of the Faculty of Agriculture, University for Development Studies, Nyankpala, to evaluate the growth and yield responses of cowpea and groundnut to five rhizobial inoculant strains in the Guinea Savanna zone. The experiment was laid out in a randomized complete block design (RCBD) with eight (8) treatments replicated four (4) times. The treatments included five rhizobial inoculant strains (NC 92, KNUST 1002, KNUST 1003, KNUST 1006, and BR 3267), two N fertilizer levels (20 kg·N/ha and 40 kg·N/ha), and a control. The results showed that rhizobial inoculation and N fertilizer application increased nodulation, biomass yield, pod number, pod weight, hundred seed weight, nodule dry weight, and pod yield of groundnut compared with the control. Rhizobial inoculation averagely increased the nodulation and yield by 63 and 67%, respectively, compared with the control. Mineral N fertilizer (20 kg N/ha) on average increased the nodulation and yield by 24 and 25%, respectively, compared with the control plots. It can be recommended from this study that, in the absence of highly competitive rhizobial strains such as KNUST 1006 and NC 92 as biofertilizers for increasing the nodulation and yield of cowpea and groundnut, 20 kg·N/ha can be used for the purpose. Further research is recommended using these rhizobial strains in combination with lower rates of N fertilizers (<20 kg·ha−1).