The topical and noninvasive measurement of high-density surface electromyogram (HD-sEMG) signals enables the estimation of human motor unit action potentials (MUAPs) as crucial motor function indicators for human-robot interaction. In this article, we present a 2-D high-density microneedle electrode array using the potassium hydroxide (KOH) bulk etching technique and the flexible printed circuit (FPC). To determine the optimal configuration of the 2-D electrode array, we propose an accurate and efficient neuromuscular analytical model for HD-sEMG that comprehensively analyzes the effects of the microneedle electrode size, interelectrode distance, and location. The experiment was conducted to demonstrate the feasibility and performance of the proposed microneedle-based high-density electrode array for the sEMG-based upper limb exoskeleton’s elbow joint angle estimation, specifically in comparison to a commercial wet electrode. The experimental results showed that the proposed microneedle electrode with high spatial resolution was comparable to the wet electrode (Wilcoxon rank-sum test, $p \gt 0.05$ ). On average, the correlation and root-mean-squared error (RMSE) of the microneedle electrode array with high space utilization were 7.56% and 19.83% better than those of the wet electrode, respectively. The 2-D high-density microneedle electrode array based on the proposed HD-sEMG model facilitates a novel neural-machine interface for intuitive control of upper limb exoskeletons.