Maleic anhydride is an important raw material in many chemical reactions, and very often, condensation is required to reflux maleic anhydride back to the reactor. It has been shown that severe fouling occurs to the maleic anhydride condenser, which is a major challenge to the operation in chemical plants. Clearly, an efficient mitigation plan is highly dependent on the understanding of the underlying mechanisms. However, the mechanisms of the fouling in the maleic anhydride condenser remain unclear to date. Here we report our experimental efforts in (1) uncovering the governing mechanisms of the fouling in maleic anhydride condensers and (2) developing the strategy to combat the condenser fouling. Our in-situ interface characterization and H-1 NMR results suggest that the condensed maleic anhydride, which is a liquid, is pinned on the condenser surface and thus reacts with the trace amounts of water to produce maleic acid, which is a solid. The maleic acid solid particles accumulate on the condenser surface and over a short period of time, i.e., days to weeks, will plug the condenser tubes. The key enabler of this process is that the maleic anhydride droplets are pinned on the tube surface and do not roll off the surface, which results from the high roughness of the condenser surface. We found that, after the surface roughness is reduced by machining, the maleic anhydride droplets roll off the tube surface much more easily, indicating this is a promising approach to reduce the condenser fouling.