Epoxides have many primary and secondary atmospheric sources. As with other oxygenates, they exhibit a complex temperature-dependent reaction with OH, whose full description is necessary in order to understand their interactions in atmospheric and combustion environments. We measured the kinetics of the title reaction using two complementary absolute methods: pulsed-laser photolysis–laser-induced fluorescence (PLP–LIF) and a discharge-flow mass spectrometric system (DF-MS), both monitoring temporal decays in OH. In addition, two relative methods employing the DF-MS as a function of temperature as well as several simulation chamber experiments at room temperature were performed. A very weak negative temperature dependence was observed at T ≤ 285 K, and only through the combination of precise data and a large temperature range were we able to discern the transition toward positive temperature dependence found at T ≥ 295 K. The non-Arrhenius temperature dependence of OH + 1,2-epoxybutane implies the agency of prereactive complexes in this reaction mechanism, albeit with a smaller effect than that with its acyclic ether analogues. This will have implications for understanding the chemical fate of epoxides within oxidizing environments.