Polyurethane (PU) is a good candidate to be used as conformal coatings for space electronic components and boards due to its manufacturability and desirable mechanical properties. It also keeps tin whiskers from growing on the tin-rich surfaces under a long-term usage that will ultimately result in electrical failure. PU coating can, however, be susceptible to the irradiation damage in space environment that ultimately alters its chemical structure and mechanical behavior. In this study, four variations of PU-based coatings (PU filled with and without nanosilica particles; polyurethane acrylate (PUA) filled with and without nanosilica particles) were investigated to understand the irradiation damage on chemical structure and the corresponding mechanical properties under three electron beam irradiation fluences (1 × 1014 cm−2, 1 × 1015 cm−2, 1 × 1016 cm−2). Infrared spectroscopy was used to examine the degradation of chemical bonding with irradiation. Microphase separation, the degree of curing, and molecule chain mobility were examined via differential scanning calorimetry (DSC) by monitoring the shift in glass transition temperatures after the irradiation. The electron beam irradiation on PU films resulted in the quinone structure formation whereas, on PUA film, microphase separation increased, thereby making both films stronger and stiffer, but less ductile and more brittle. As a result, PU and PUA coatings under a high fluence of irradiation will be more prone to tin whisker penetration. This study also shows the potential effect of nanosilica on retarding the irradiation damage in PU and PUA films.