Oxygen vacancies in transition-metal oxides facilitate catalysis critical for energy storage and generation. However, promoting vacancies at the lower temperatures required for operation in devices such as metal-air batteries and portable fuel cells has proven elusive. Here we used thin films of perovskite-based strontium cobaltite (SrCoOx) to show that epitaxial strain is a powerful tool for manipulating the oxygen content under conditions consistent with the oxygen evolution reaction, yielding increasingly oxygen-deficient states in an environment where the cobaltite would normally be fully oxidized. The additional oxygen vacancies created through tensile strain enhance the cobaltite's catalytic activity toward this important reaction by over an order of magnitude, equaling that of precious-metal catalysts, including IrO2. Our findings demonstrate that strain in these oxides can dictate the oxygen stoichiometry independent of ambient conditions, allowing unprecedented control over oxygen vacancies essential in catalysis near room temperature.