The reaction pathways and phase evolution during synthesis of CuInSe2 (CIS) by a novel bilayer approach were investigated using in situ high‐temperature X‐ray diffraction. Two bilayer precursor structures, glass/Mo/γ‐In2Se3/β‐CuSe + β‐Cu2Se/Se and glass/Mo/γ‐In2Se3/β‐Cu2Se/Se, were examined in this study. Temperature ramp experiments revealed that the phase transformation sequence for each bilayer precursor qualitatively follows that predicted by the phase diagram and that the onset temperatures for decomposition of the sub‐binary compounds depend on the Se partial pressure. Measurement of the isothermal rate of formation of CuInSe2 at six temperatures in the range 260 to 310 °C for the γ‐In2Se3/β‐CuSe + β‐Cu2Se/Se bilayer suggests relatively slow nucleation followed by diffusion‐limited reaction with estimated activation energy of 162(±7) and 225 (±16) kJ/mol from Avrami and parabolic models, respectively. Interestingly, the measured activation energy for the same precursor in a 4 mol % H2/He ambient (108 (±8) kJ/mol) was lower than that observed in pure N2 (158 (±16) kJ/mol). The results of isothermal measurements in the temperature range 250 to 300 °C for the γ‐In2Se3/β‐Cu2Se/Se precursor film in an inert ambient are consistent with one‐dimensional diffusion‐limited growth with estimated activation energy from the Avrami and parabolic models of 194 (±10) and 203 (±12) kJ/mol, respectively. Copyright © 2012 John Wiley & Sons, Ltd.