The thermal properties of nine biologically important fused azaisocytosine-containing congeners, e.g. 3-(thiophen-2-yl)-8-(R-phenyl)-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (1-9), were studied by means of different thermal analysis methods (TG-DTG-DSC and TG-FTIR). The influence of heating atmosphere (air and nitrogen) on the pathways of thermal decomposition was investigated. The thermal stability of the investigated compounds in air can be ordered (in relation to the substituent attached at the phenyl moiety and denoted as R) as follows: 2-CH3O < 2-CH3 < 2,3-(CH3)2 ≈ 2-Cl = 4-CH3 < H ≈ 3-Cl = 4-Cl ≈ 3,4-Cl2. The two-stage thermal decomposition of compounds 1–9 in air was preceded by the melting process. One significant mass loss was observed during compounds pyrolysis under nitrogen atmosphere. The main volatile products of compounds degradation such as: carbon oxides, carbon oxysulfide, ammonia, isocyanic acid and its derivatives as well as methane and aromatic hydrocarbons were identified by the FTIR spectra. The impact of substituent types on the thermal behaviour of the studied congeners was described. The crystal structure of 8-(2-methoxyphenyl)-3-(thiophen-2-yl)-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one (5) was determined by the single-crystal X-ray diffraction method.