In natural gas pipeline transportation, the deposition of liquid droplets entrained in the gas could lead to an increase in the transportation resistance and other problems, such as equipment damage and corrosion. Liquid impurities in the gas can be effectively separated by coalescing filtration. However, higher efficiency leads to higher resistance for filter media. To meet the demand for developing high-efficiency and low-resistance filter media for industrial processes, glass fiber filter media as the substrate were used in this study. Patterned filter media with non-uniform wettability were prepared via surface modification. The effects of strip pattern arrangement, pattern spacing and number, and the number of filter material layers on the filtration performance were investigated. The results showed that the pressure drop could be reduced for filter media with staggered and overlapped arrangements of the modified areas. More dispersed oleophobic areas led to a more significant reduction of the pressure drop. When the pattern spacing was 5 mm and the number of patterns was 16, the filter media had the lowest saturation and steady-state pressure drop, and the steady-state pressure drop was reduced by 37% compared with that of the untreated filter media. For multi-layer patterned filter media, when the number of layers was the same, the liquid transport path in the filter media with the optimal pattern arrangement was shorter, resulting in a more significant decrease in pressure drop.