Cross-laminated timber (CLT) panels have potential market in North America for building mid-rise or even taller structures due to their good structural and fire safety performance, light weight, and prefabricated nature. However, to ensure long-term durability when used in building enclosures, the hygrothermal performance of CLT wall assemblies needs to be evaluated in terms of wetting and drying potential. A test wall consisting of sixteen 0.6 m by 0.6 m CLT panels made of five different wood species (or species groups) and four different wall assemblies was constructed. The CLT panels were initially wetted with the moisture content (MC) in the surface layers approaching or exceeding 30%, and monitored for MCs and temperatures at different depths over one year in a building envelope test facility located in Waterloo, Ontario. The drying behaviour of these panels was analysed and the measured MCs over time were compared to simulation results using a commercial hygrothermal program. This field study showed that most of the CLT panels dried to below 26% within one month except for CLT walls with a low-permeance interior membrane, which indicated that none of the CLT walls would likely remain at a high MC level long enough to initiate decay under the conditions tested. The simulation results generally agree well with the field data at MCs below 26%. However, it was found that the hygrothermal simulation program tended to overestimate the MC in the centre of the panels by up to 5e10%, and simulated MCs at locations deep into the CLT panels were not as responsive to changes in ambient conditions, as the measurements indicated for assemblies with high exterior permeance.