Human manganese superoxide dismutase (MnSOD) is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers (CPETs) are used by the enzyme to rid the mitochondria of O2•−, a precursor to other harmful reactive oxygen and nitrogen species. The mechanisms of CPET-utilizing enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules involved in catalysis while controlling the redox state of the enzyme. Here, neutron diffraction of redox-controlled MnSOD crystals revealed the all-atom structures of Mn3+SOD and Mn2+SOD delivering unique data on sites of differential protonation. A novel mechanism is proposed from the direct observation of glutamine deprotonation, the involvement of Tyr and His with altered pKas, and three unusual strong-short hydrogen bonds that change with the oxidation state of the metal. Quantum calculations provide insight into the electronic modulation of the observed structures.