The growing demand for long-distance green methanol transportation highlights the critical need to evaluate the safety and reliability of pipeline sealing materials. This study investigates the swelling mechanisms of fluorocarbon rubber (FKM), nitrile butadiene rubber (NBR), and polytetrafluoroethylene (PTFE) under simulated methanol pipeline conditions. Static immersion tests were conducted under simulated pipeline conditions with water contents of 0–20% and temperatures of 25–55 °C, supplemented by thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and gas chromatography–mass spectrometry (GC–MS). FKM exhibited severe physical swelling, with the volume increase reaching up to 80% in pure methanol. Notably, the addition of 5% water markedly suppressed this swelling, reducing the volume change of FKM sealing rings to approximately 3% and the mass change to 1%. Conversely, NBR experienced volume shrinkage and mass loss due to the extraction of the plasticizer Bis(2-ethylhexyl) phthalate by methanol, a process also inhibited by water. PTFE demonstrated exceptional chemical stability and negligible dimensional changes owing to its high crystallinity and rigid structure. Consequently, PTFE is recommended as the optimal sealing material for pure methanol pipelines. When utilizing FKM or NBR, strict control over the fluid’s water content and operating temperature is essential to prevent degradation and ensure long-term pipeline integrity.