Transition metal sulfides have been demonstrated to be more active electrocatalysts than the corresponding (hydr)oxides for oxygen evolution reaction (OER). The nature of active sites, however, remains unclear. Here, we study whether S could promote the OER activity of FeCoOOH and try to identify the catalytically active centers. Density functional theory suggests that two coordinating S could work synergistically with one adjacent Fe to optimize the electronic states of Co, resulting in decreased binding energy of OH∗ (ΔEOH) while little changed ΔEO, and thus significantly lowering the catalytic overpotential. Further experimental studies validate the synergistic effect between S and Fe on tuning the electronic structure and the greatly improved catalytic activity with a small overpotential of 225.3 mV to drive 20 mA cm−2. This study reveals the origin of the high catalytic activity of transition metal sulfides and provides insights into the design of efficient OER electrocatalysts. Yuan et al. study the effect of S on the OER activity of FeCoOOH. Results show that two coordinating S and one adjacent Fe synergistically optimize the electronic states of Co, resulting in the decreased binding energy of OH∗ (ΔEOH), with little change to ΔEO, thus greatly enhancing the catalytic activity.