The oxidation of tetrahydropyran (THP) was investigated in two atmospheric jet-stirred reactors over temperatures of 450–900 K and equivalence ratios of 0.25–1.0. Utilizing synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS) and gas chromatography (GC) methods, we qualitatively and quantitatively analyzed dozens of intermediates, including C1-C4 carbonyl compounds, conjugated olefins, cyclic ethers, and reactive hydroperoxides. This comprehensive analysis provided insights into the cool flame chemistry of THP. For the first time, we observed remarkable low-temperature oxidation reactivity and negative temperature coefficient (NTC) behavior during THP oxidation. Quantum chemistry calculations, including adiabatic ionization energy and appearance potential energy calculations, were performed to identify reaction products. Additionally, energy barrier analysis of key reactions allowed an exploration of the effects of the ether group in intramolecular H-transfer. Our proposed model introduces a conformational-dependent THP oxidation sub-mechanism, enhancing predictability and highlighting the intricate low-T chemistry of THP. Rigorous validation against current and literature experimental data across diverse conditions demonstrated high accuracy. We found that the ether group in the heterocycle ring can enhance C-H bond energy at its meta-sites and weaken C-H bond energy at its ortho-sites of key radicals (e.g., ROO, OOQOOH). In the low-T region, β-tetrahydropyranyl preferentially undergoes chain inhibition, while chain-branching reactions become more favorable for reaction sequences originating from α- and γ-tetrahydropyranyl. With increasing temperature, the ring-opening of α- and β-tetrahydropyranyl radicals becomes more competitive, leading to a pronounced NTC behavior in THP oxidation.