This study evaluated the performance of an upflow anaerobic filter (UAF) reactor in the thermophilic methane fermentation of hypersaline molasses wastewater. The high salinity (similar to 45 mS/cm) of the undiluted wastewater completely inhibited the biogas production. An acclimation strategy involving gradient dilution of the molasses wastewater was implemented to gradually increase the salt stress. Consequently, the biogas production was recovered, inhibited only slightly by the high salinity of the undiluted wastewater. The reactor steadily achieved a high total organic carbon (TOC) loading rate of 5 g/L/day, with approximately 60% TOC removal efficiency. Acclimation to the gradually increased salt stress leads to a relative abundance of some halotolerant microbes, such as bacteria from Arcobacter, Tissierella, and Ruminococcaceae, which increased as their hydrolytic and acidogenic abilities adjusted to the incremental increase in salinity. Additionally, hydrogenotrophic methanogens, especially Methanoculleus, showed greater resistance to hypersalinity than aceticlastic methanogens. These results suggest that acclimation of the fermentation microbial community to hypersalinity is an effective strategy to improve methane production from hypersaline molasses wastewater in thermophilic UAF reactors.