For the first time, we directly measured the onset and completion temperatures of polymorphic transitions under thermo-mechanochemical conditions by simultaneous in situ synchrotron powder X-ray diffraction and temperature monitoring. We determined the thermo-mechanochemical polymorphic transition temperature in 1-adamantyl-1-diamantyl ether to be 31 °C lower than the transition temperature determined by DSC. Our findings highlight the uniqueness of thermo-mechanochemical conditions, with potential applications in polymorph screening.