This paper presents the results of the first experimental thermochemical investigation of two natural trioctahedral chlorites (clinochlores). The study was performed with the help of a high-temperature heat-flux Tian-Calvet microcalorimeter. The samples were characterized by X-ray spectroscopy analysis, X-ray powder diffraction, thermal analysis, and FTIR spectroscopy. The enthalpies of formation of clinochlores were found using the melt solution calorimetry method to be: −8806 ± 16 kJ/mol for composition ( Mg 4 . 9 Fe 0 . 3 2 + Al 0 . 8 ) [ Si 3 . 2 Al 0 . 8 O 10 ] ( OH ) 8 and −8748 ± 24 kJ/mol for composition ( Mg 4 . 2 Fe 0 . 6 2 + Al 1 . 2 ) [ Si 2 . 8 Al 1 . 2 O 10 ] ( OH ) 8 The experimental data for natural samples allowed calculating the enthalpies of formation for end-members and intermediate members of the clinochlore (Mg 5 Al)[Si 3 AlO 10 ](OH) 8 and chamosite (Fe 5 Al)[Si 3 AlO 10 ](OH) 8 series. An important feature of the clinochlore structure is the presence of two distinct hydroxyl-containing octahedral layers: the interlayer octahedral sheet and octahedral 2:1 layer; the enthalpies of water removal from these positions in clinochlore structure were determined as: 53 ± 20 kJ/(mol·H 2 O) and 131 ± 10 kJ/(mol·H 2 O), respectively. These obtained first thermodynamic characteristics of Mg-Fe clinochlores can be used for quantitative thermodynamic modeling of geological and industrial processes including clinochlores of different composition.