Growth behavior and microstructure of oxide scale formed on MoSi2 coating by cyclic oxidation testing in air at 500 °C were investigated using field emission scanning electron microscopy, cross-sectional transmission electron microscopy, glancing angle x-ray diffraction, and x-ray photoelectron spectroscopy. MoSi2 coating was prepared by chemical vapor deposition of Si on a Mo substrate at 1100 °C for 5 h using SiCl4–H2 precursor gas mixtures. After the incubation period of about 454 cycles, accelerated oxidation behavior was observed in MoSi2 coating and the weight gain increased linearly with increasing oxidation cycles. Microstructural analyses revealed that pest oxide scale was formed in three sequential processes. Initially, nanometer-sized crystalline Mo4O11 particles were formed with an amorphous SiO2 matrix at MoSi2 interface region. Inward diffusing oxygen reacted with Mo4O11 to form Mo9O26 nano-sized particles. At final stage of oxidation, MoO3 was formed from Mo9O26 with oxygen and growth of MoO3 took place forming massive precipitates with irregular and wavy shapes. The internal stress caused by the growth of massive MoO3 precipitates and the volatilization of MoO3 was attributed to the formation of many lateral cracks into the matrix leading to pest oxidation of MoSi2 coating.