For thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs), the emitters are randomly dispersed into an isotropic host matrix to avoid luminescence quenching and exciton annihilation, making it extremely challenging to optimize molecular orientations for further improving the out-coupling efficiency. In this study, we first demonstrate that the molecular orientations of the DMAC-TRZ and spiroAC-TRZ, two typical donor−acceptor structured TADF emitters, can be substantially changed by different guest− host contact modes during vapor depositions. When the acceptor unit is docked into the host film surface, the emitter molecules appear to be oriented more vertically. By contrast, the donor−host surface contacts facilitate more horizontal molecular orientations. Therefore, we designed two emitters, named the 3DMAC-TRZ and 3spiroAC-TRZ, with three donor units linking to and surrounding the TRZ unit. Consequently, detrimental acceptor−host contacts are prohibited, and horizontal orientations are substantially enhanced for the 3DMAC-TRZ and 3spiroAC-TRZ. Overall, our work highlights that selectively controlling the guest−host contact modes during the depositions is an effective way to modulate the emitter's horizontal orientation toward efficient optical out-couplings for TADF OLEDs.