Local muscle fatigue (LMF) is a common physiological phenomenon that occurs in daily exercise training and medical rehabilitation. Without timely treatment it can easily lead to muscle spasm, ligament rupture, and even stress fractures. Electrical impedance myography (EIM) is a noninvasive bioelectrical impedance technique suitable for the wearable LMF monitoring anytime and anywhere. In this paper, a novel EIM electrode configuration was proposed by establishing a four-layer simulation model of the human upper arm in FEM software. Sensitivity parameters were introduced to optimize muscle selectivity. The effect of fat thickness on impedance change rate was explored to reduce the influence of individual fat differences on EIM results. Dynamic and static contraction experiments of muscle fatigue were performed on the biceps brachii muscles of 10 volunteers to verify the effectiveness and feasibility of the proposed electrode configuration. The proposed electrode configuration reduced the measurement area by 25%, whereas the impedance amplitude and sensitivity remained the same. The influence of individual fat differences on EIM results was significantly reduced. When the fat thickness increased from 6 mm to 18 mm, the impedance change decreased by 31.78% compared with the traditional electrode configuration. When the muscles were extremely exhausted, the decrease in resistance varied around 10 Ω and within 10-1 order of magnitude in different volunteers. In a word, the proposed electrode configuration effectively evaluated the degree of LMF, providing more feasibility for the design of wearable devices. INDEX TERMS Electrical impedance myography, local muscle fatigue, optimized electrode configurations, finite element method, the biceps brachii muscles.