The capability to actively control chemical reactions has enormous implications for energy generation and conversion. By integrating theory and experiments, we achieved an in-situ regulation of formic acid oxidation on a Pt (1 1 1) surface via externally applied strains. The first-principles theory predicted that compressive strains can lower the reaction overpotential to boost the formate pathway and alleviate CO poisoning on the Pt surface, while tensile strains should have the opposite effects. The experimental observations confirmed the theoretical predictions. Compressive elastic strains (approximately -0.4%) could create over 75 mV overpotential decrease, far beyond what was achieved in previous works. A mass activity (similar to 700 mA/mg) of Pt was achieved in a broad potential range of 0.4-0.85 V (vs RHE) under compressive strains. There was no evident activity loss during the chronoamperometry test at 0.6 V. The first-principles theory, controlled synthesis and in-situ measurements were combined to achieve active control, which represents important progress in tuning the electrocatalytic activity of formic acid oxidation. (C) 2020 Elsevier Inc. All rights reserved.