Triboelectrification mechanism is still not understood, despite centuries of investigations. Here, we propose a model showing that mechanochemistry is key to elucidate triboelectrification fundamental properties. Studying contact between gold and silicate glasses, we observe that the experimental triboelectric output is subject to large variations and polarity inversions. First principles analysis shows that electronic transfer is activated by mechanochemistry and the tribopolarity is determined by the termination exposed to contact, depending on the material composition, which can result in different charging at the macroscale. The electron transfer mechanism is driven by the interface barrier dynamics, regulated by mechanical forces. The model provides a unified framework to explain several experimental observations, including the systematic variations in the triboelectric output and the mixed positive-negative “mosaic” charging patterns, and paves the way to the theoretical prediction of the triboelectric properties.

The lack of theoretical understanding of triboelectrification has hindered the development of energy harvesting technologies like triboelectric nanogenerators. Focusing on polytetrafluoroethylene, a material with a strong triboelectric output, a model predictive of its triboelectric behavior, driving the development of improved nanogenerators are formulated. With a combined computational‐experimental approach it is shown that defluorination enhances polytetrafluoroethylene nanoscale triboelectric charging. Then a model, explaining the macroscale triboelectric output as determined by the competition of two mechanisms is developed. Defluorination enhances charging while also reducing the interface gap, favoring the backflow of electrons, and possibly reducing charging. However, numerical analysis shows that backflow is negligible, aligning with the prediction of increased triboelectric output. By building triboelectric nanogenerators with defluorinated polytetrafluoroethylene samples, achieved by X‐ray irradiation, a one‐order‐of‐magnitude output increase is demonstrated. The predictive models, supported by experiments, lead to an improved strategy for designing effective energy harvesting devices and new applicative breakthroughs.