Usage of pure tin (Sn) or Sn-rich alloy in electronics industry is growing, which makes them more susceptible to the spontaneous growth of tin whiskers. The risk of having these whiskers can be dramatically mitigated by applying a conformal coating such as parylene C. The purpose of this paper is to investigate the degradation of parylene C coating (with two thicknesses, 12.5 μm and 25 μm) during thermal aging in high humidity environment (85 °C/85% relative humidity for up to 5000 h) and its effect on the tin whisker mitigation property. It was observed that under the high temperature and high humidity (HTHH) environment, the oxidation occurs at early times, followed by bond scission, resulting in the loss in strength and modulus of the parylene coating. After 2500 h of aging, due to the degradation of the silane agent at the tin/parylene interface, the adhesion of the parylene coating on the tin surface was significantly weakened, which resulted in extensive corrosion of the tin solderpads. The loss of adhesion of the coating, along with the corrosion of the tin surface facilitated tin whisker nucleation at the interface while the loss of mechanical strength and the brittleness made the growing whiskers penetrate easily through the coating. Tin whiskers with a smaller diameter were buckled and grew along the delaminated interfacial region while those with a larger diameter penetrated and continued to grow through the coating. Although the thicker parylene coating helped delay the complete penetration and increase the critical diameter of whiskers for complete penetration, it showed more tin whisker activities and easy penetration by large diameter whiskers due to poorer adhesion. Hence, the effectiveness of the parylene coating on tin whisker mitigation will depend on its degradation kinetics of mechanical properties and adhesion under such harsh conditions.