With the increasing demand for freshwater, desalination of seawater and its alternatives has become a major priority for the scientific community. This work studied the preparation of a flat-sheet poly(vinylidene fluoride) (PVDF)/poly(methyl methacrylate) (PMMA) composite membrane by non-solvent induced phase separation (NIPS) for desalination using membrane distillation. The casting dope comprises PVDF, PMMA, and dimethyl sulfoxide (DMSO) in accordance with the green chemistry principle. The effect of PMMA content ranging from 3.6 wt% to 14.4 wt% in the casting dope on the membrane morphologies and characteristics was investigated. For a better understanding of membrane distillation, the performance of air gap membrane distillation (AGMD) and water gap membrane distillation (WGMD) at different feed temperatures (50–70 °C), flow rates (0.4–0.8 L/min), and gap widths (∼0, 1, 3 mm) were analyzed. Additionally, the advantages and disadvantages of DCMD and WGMD were evaluated using the permeate flux and gained output ratio (GOR). According to the results of the experiments, with an increase in PMMA content, the pore size, porosity, and contact angle of the membrane increased while the thickness of the skin layer decreased. In addition, the permeate fluxes were found to be greater in WGMD than in AGMD due to the higher thermal conductivity of water relative to air. The flux of membrane distillation increased as the gap width decreased and the feed temperature and flow rate increased. The highest flux of WGMD is 26.04 L m−2 h−1 when the feed temperature is 70 °C, the flow rate is 0.8 L/min, and the gap width is ∼0 mm. With optimal operating conditions, the as-prepared membrane showed potential for desalination, offering a viable solution to water stress concerns.