Hydrogenase enzymes use Ni and Fe to oxidize H2 at high turnover frequencies (TOF) (up to 10 000 s−1) and low overpotentials (<100 mV). In comparison, the fastest reported synthetic electrocatalyst, [NiII(PCy2NtBu2)2]2+, oxidizes H2 at 60 s−1 in MeCN under 1 atm H2 with an unoptimized overpotential of ca. 500 mV using triethylamine as a base.1 Here we show that a structured outer coordination sphere in a Ni electrocatalyst enhances H2 oxidation activity: [NiII(PCy2NArg2)2]8+ (Arg=arginine) has a TOF of 210 s−1 in water with high energy efficiency (180 mV overpotential) under 1 atm H2, and 144 000 s−1 (460 mV overpotential) under 133 atm H2. The complex is active from pH 0–14 and is faster at low pH, the most relevant condition for fuel cells. The arginine substituents increase TOF and may engage in an intramolecular guanidinium interaction that assists in H2 activation, while the COOH groups facilitate rapid proton movement. These results emphasize the critical role of features beyond the active site in achieving fast, efficient catalysis.