Thermal resistance is a very important parameter when assessing the therapeutic usefulness of potential pharmaceutics. Therefore, the thermal behaviour and the decomposition mechanism in the atmosphere of helium and synthetic air of disubstituted fused 1,2,4-triazoles—which may be potential anticancer and antibacterial agents—were studied with a use of simultaneous thermal analysis: thermogravimetry/differential scanning calorimetry (TG/DTG/DSC) coupled online with Fourier transform infrared spectroscopy. It was confirmed that the thermal stability of the tested compounds is directly depended on their structure and thus on the number of chlorine atoms as substituents. The pyrolysis process of disubstituted fused 1,2,4-triazoles in inert conditions runs in two main, non-well-separated stages connected with the emission of NH3, HCN, acetonitrile, aromatics with an OH group, aromatics with a NH2 groups, H2O, CO2 and alkene fragments. However, the thermal stability of those compounds in synthetic air atmosphere is comparable or lower than their thermal stability in helium atmosphere. The decomposition of the tested compounds runs through at least three main stages, resulting in the emission of the same type of volatiles as in inert conditions plus the additional emission of CO and some carbonyl fragments for compounds with no or one chlorine atom as a substituent. The results indicate a simultaneous cleavage of C–N, N–N and C–O bonds during heating of the tested disubstituted fused 1,2,4-triazoles in inert conditions and additional combustion process of pre-formed residues in oxidative conditions.