Membrane fouling and pore wetting are the key problems affecting the separation performance of membrane distillation (MD). They can become more severe with increasing the operation time, which will have a negative impact on heat and mass transfers. In this paper, solutions containing CaCO3, humid acid (HA), and/or silica sols (SiO2) were used as the feed with different Hyflon AD/polyvinylidene fluoride (PVDF) composite membranes for vacuum membrane distillation (VMD). The evolutions of flux and salt rejection during the concentration process were examined, and the membranes with different properties were compared. The results showed that the original membrane was more prone to be fouled and wetted even at low concentration factors. In the single component systems, CaCO3 impacts the membrane performance most severely. With the hybrid component solutions, the flux declines for the composite membranes were lower than that of the original membrane. Compared with the single-component systems, the practical situation is more likely close to the hybrid-component system where fouling and wetting were easier to happen. Overall, the composite membranes showed enhanced fouling and wetting resistance and maintained stable salt rejections. Particularly, the composite membrane with smaller pore sizes (M-40L) performed best among all the membranes, suggesting its high potential for practical VMD applications.