The primary objective of this research was to assess and to model the hygrothermal properties of CLT panels made from three distinct combinations of spruce lumber and laminated strand lumber (LSL). The hygrothermal performance of these materials both individually and in conjunction in CLT has not been investigated before and is an important indicator of CLT building wall performance. CLT panels consisting of spruce as a face layer absorbed moisture more rapidly when that face layer was exposed to higher moisture concentration compared to CLT panels consisting of LSL as a face layer. The accumulation of moisture between layers increased with placement of the LSL as a core layer. Based on the smaller diffusion coefficient, moisture transport through the CLT panels made of LSL was slower. Modelling with a finite element-based program showed that the temperature in the panels when exposed to a severe gradient equilibrated within two days, as shown by both experimental and simulated results. For moisture transfer, the diffusion coefficient variation with moisture content and temperature based on the Arrhenius equation produced simulation results in agreement with experimental results but the moisture transfer was much slower than the heat transfer.