<p>Quantum effects in chemical reactions are most pronounced at ultracold temperatures, where only a few partial waves contribute. While interference among many partial waves is theoretically expected to persist at higher temperatures, direct evidence for such quantum effects in reactive processes has been lacking. Here, we report signatures of quantum interference suppressing a chemical reaction in the multi-partial-wave regime: resonant charge exchange between a single ⁸⁷Rb⁺ ion and its parent atom ⁸⁷Rb. Using quantum-logic detection on a single atom-ion pair and a calibrated in-situ measurement of Langevin collision probabilities, we benchmark the thermally averaged reaction rate against both classical and quantum predictions. We find that the reaction rate is suppressed by over an order of magnitude relative to the classical expectation, despite occurring in the millikelvin temperature regime (more than three orders of magnitude above the <i>s</i>-wave threshold), where more than a dozen partial waves contribute. These results suggest quantum interference as a key mechanism in chemical reactivity beyond the ultracold limit and offer a platform for probing coherent quantum effects in atom-ion reactions where ab initio methods remain intractable.</p>