Poly(oxymethylene) dimethyl ethers (OME) reduce soot formation during the combustion process when added to diesel fuels. OME are a gas-to-liquid option as they can be produced via methanol from natural gas or renewable feedstocks. This work deals with the synthesis of OME from the educts formaldehyde and methanol in aqueous solutions. The studied mixtures are complex reacting systems in which, poly(oxymethylene) glycols and poly(oxymethylene) hemiformals), in addition to OME are present. The chemical equilibrium of OME formation is studied in a stirred batch reactor in which the educts overall ratio of formaldehyde to methanol, the amount of water, and the temperature (333.15 and 378.15 K) varies. A mole fraction-based and an activity-based model of the chemical equilibrium of the OME formation are developed, which explicitly account for the formation of poly(oxymethylene) glycols and poly(oxymethylene) hemiformals. Information on the latter reactions from the literature are confirmed by NMR experiments in the present work.