The interfacial layer (IL) in organic solar cells (OSCs) can be an important boosting factor for improving device efficiency and stability. Herein, a facile and cost-effective approach to form a uniform molybdenum oxide (MoO3) film with desirable stability is provided, based on solution processing at low temperatures by simplified precursor solution synthesis. The solution-processed MoO3 (SM) film, with oxygen vacancies induced by the hydroxyl group, functions as an efficient anode IL in conventional OSCs. The hole-transporting performance of SM is well demonstrated in nonfullerene-based OSCs exhibiting over 10% of power conversion efficiency. The enhanced device performance of SM-based OSCs over that of poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is investigated by analyzing the morphology, electronic state, and electrical conductivity of such a hole-transporting layer, as well as the charge dynamics in the completed devices. Furthermore, the high stability of the SM films in OSCs is examined under various environmental conditions, including long-term and thermal stability. In particular, fullerene-based OSCs with SM maintain over 90% of their initial cell performance over 2500 h under inert conditions. It is shown that solution-processed metal oxides can be viable ILs with high functionality and versatility, overcoming the drawbacks of conventionally adopted conducting polymer interlayers.