The reactivity of carbonyl oxides has previously been shown to exhibit strong conformer and substituent dependencies. Through a combination of synchrotron-multiplexed photoionization mass spectrometry experiments (298 K and 4 Torr) and high-level theory [CCSD(T)-F12/cc-pVTZ-F12//B2PLYP-D3/cc-pVTZ with an added CCSDT(Q) correction], we explore the conformer dependence of the reaction of acetaldehyde oxide (CH₃CHOO) with dimethylamine (DMA). The experimental data support the theoretically predicted 1,2-insertion mechanism and the formation of an amine-functionalized hydroperoxide reaction product. Tunable-vacuum ultraviolet photoionization probing of anti– or anti– + syn-CH₃CHOO reveals a strong conformer dependence of the title reaction. The rate coefficient of DMA with anti-CH₃CHOO is predicted to exceed that for the reaction with syn-CH₃CHOO by a factor of ∼34,000, which is attributed to submerged barrier (syn) versus barrierless (anti) mechanisms for energetically downhill reactions.