AbstractThe performance of single‐atom electrocatalysts usually suffers from attenuation due to high energy states, especially in harsh environments. Therefore, as high‐efficiency electrocatalysts for hydrogen reduction reaction (HER), supported metal nanoclusters (NCs) with maximum metal atom efficiency are promising, yet the genuine mechanism involving rational orbital modulation is still arguable. Herein, the conjugating effect between electron‐donor boron (B)‐tethering engineering and iridium (Ir) that facilitates the electron capture of Ir atoms is explored, achieving highly dispersive Ir‐NCs confined in N, B co‐doped defective carbon (Ir@NBD‐C). The Ir@NBD‐C catalyst achieves displays remarkable high activity for HER in a pH‐universal range, in particular, with an ultralow overpotential of 7 mV (10 mA cm⁻²), high mass activity of 652.2 A , and turnover frequency (TOF) of 1.90 H₂ S⁻¹ (100 mV) in 1.0 m KOH, outperforming almost all state‐of‐the‐art HER electrocatalysts. Operando characterizations and theoretical calculations unveil that the outstanding catalytic activity can attribute to the optimal binding to hydrogen intermediate species (H^*) derived from the tunable and favorable electronic structure of the Ir site through the tethering of B heteroatoms. Undoubtedly, this work brings new insight into the design of catalysts with high intrinsic activity and thermodynamic stability.