It is now well established that many of the technologically important properties of two-dimensional (2D) materials, such as the extremely high carrier mobility in graphene and the large direct band gaps in MoS2 monolayers, arise from quantum confinement. However, the influence of reduced dimensions on electron–phonon (e–ph) coupling and its attendant dephasing effects in such systems has remained unclear. Although phonon confinement is expected to produce a suppression of e–ph interactions in 2D systems with rigid boundary conditions, experimental verification of this has remained elusive8. In this article, we show that the e–ph interaction is, indeed, modified by a phonon dimensionality crossover in layered Nb3SiTe6 atomic crystals. When the thickness of the Nb3SiTe6 crystals is reduced below a few unit cells, we observe an unexpected enhancement of the weak-antilocalization signature in magnetotransport. This finding strongly supports the theoretically predicted suppression of e–ph interactions caused by quantum confinement of phonons.