It is important to quantify nutrient requirements and optimize fertilization to improve peanut yield and fertilizer use efficiency. In this study, a multi-site field trial was conducted from 2020 to 2021 in the North China Plain to estimate nitrogen (N), phosphorus (P), and potassium (K) uptake and requirements of peanuts, and to evaluate the effects of fertilization recommendations from the regional mean optimal rate (RMOR) on dry matter, pod yield, nutrient uptake, and fertilizer use efficiency. Results show that compared with farmer practice fertilization (FP), optimal fertilization (OPT) based on the RMOR increased peanut dry matter by 6.6% and pod yield by 10.9%. The average uptake rates of N, P, and K were 214.3, 23.3, and 78.4 kg/ha, respectively, with 76.0% N harvest index, 59.8% P harvest index, and 41.4% K harvest index. The OPT treatment increased N, P, and K uptake by 19.3%, 7.3%, and 11.0% compared with FP, respectively. However, the average of yield, nutrition uptake, and harvest indexes of N, P, and K were not significantly affected by fertilization. The peanut required 42.0 kg N, 4.6 kg P, and 15.3 kg K to produce 1000 kg of pods. The OPT treatment significantly improved the N partial factor productivity and N uptake efficiency but decreased the K partial factor productivity and K uptake efficiency. The present study demonstrates that fertilizer recommendations from RMOR improve N use efficiency, and reduce N and P fertilizer application without yield loss in regions with smallholder farmers, and the corresponding estimation of nutrient requirements helps to make peanut fertilization recommendations.