This work describes the synthesis of new 4-substituted-pyrazolo[3,4-d]pyridazinones (R = C6H5, 4-F-C6H4, benzofur-2-yl, CF3, 4-NO2-C6H4) from the reaction of dicarbonylpyrazoles with hydrazine hydrate. Solid and solution-state NMR were used to unequivocally assign the structure and identification of the byproduct formed when R = 4-NO2-C6H4. Geometrical features and the intermolecular interactions of compounds were described using single crystal X-ray diffraction. The thermal behavior of the compounds was studied using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Kinetic parameters, such as the activation energy (Ea) and pre-exponential factor (A), were determined as a function of the conversion degree for the thermal decomposition of two compounds, by using the isoconversional methods of Friedman and Ozawa–Flynn–Wall (OFW). The results showed that the Ea for thermal decomposition of compound with R = CF3 is always higher than for compound with R = C6H5, independent of the model used (Friedman or OFW), indicating that the former is more stable than the latter. Furthermore, the Ea values for compounds with R = C6H5 and CF3 are practically constant for all α values from 0.1 to 0.9, indicating the existence of a single-step degradation reaction. The kinetics results also reveal the linear dependence of Ea on the pre-exponential factor. In addition, the 4-substituted-pyrazolo[3,4-d]pyridazinones studied have two types of thermal behavior: (i) a compound that passes from the glass to a liquid phase, followed by cold crystallization, and a melting transition (R = C6H5, CF3); (ii) A compound that has no melting or freezing points, only glass-transition temperatures (R = 4-NO2-C6H4). Finally, we showed that compounds with R = C6H5 and CF3 undergo amorphization during the heating cycles, reaching 48% and 74% of amorphous content, respectively.