Oxide compounds basically composed of calcium, magnesium, aluminum and silicon cations also known as CMAS, can be deposited on the surface of thermal barrier coatings (TBC) of gas turbine blades. Under certain operation conditions these compounds have been found to aggressively degrade the TBC, hence affecting the thermo-mechanical properties of the underlying component. Detailed investigation on the interaction of CMAS and the atmospheric plasma sprayed (APS) yttria-stabilized zirconia (YSZ) TBC was performed in a burner rig test facility under thermal gradient cycling conditions and at the same time CMAS deposition. This novel and unique test approach promises a coating screening and characterization test under service conditions. Variable exposure times at approximately 1250°C/1050°C surface/substrate temperatures were applied. The lifetime of the TBC was indicated by the number of thermal cycles until significant spallation occurred. X-ray spectroscopy and microstructural analyses were conducted on the cycled samples to determine the effect of thermo-chemical interactions. It was found that with extended heating period of 10 times the standard cycle, the number of sustainable load alternations heating/cooling was reduced. Interaction of CMAS and YSZ induces formation of glassy soda-silicate phase. Thermal cycling of thermo-physically mismatched TBC and glass melt causes crack formation and coating failure.