The processing of low-grade, lead-containing practical ores requires fine grinding to liberate galena and enhance flotation recovery. The ball mill is still one of the most common approaches used in industry for fine grinding. This study investigated the effect of the grinding parameters in a ball mill on the fine grinding product of galena and on flotation performance. The grinding product had a particle size below 30 μm, which was classified into +25 μm, −25 + 10 μm, and −10 μm fractions. Grinding experiments showed that modifications to the grinding concentration, media proportion, and filling ratio exerted significant effects on the yields of the +25 μm and −10 μm fractions. Flotation experiments showed that the yield of −10 μm particles negatively affected the flotation performance of galena. Discrete element method simulation results revealed that an increase in the motion velocity of the media group enhanced attrition effects during fine grinding, promoting the generation of −10 μm particles. The higher yield of −10 μm particles facilitated a smaller contact angle and smaller agglomerate size, resulting in lower recovery. To optimize the particle size distribution and improve fine-grained galena flotation recovery, it is essential to reduce the attrition of the grinding media on the mineral.