Cross-laminated timber (CLT) is a type of mass timber panel used in floor, wall, and roof assemblies. An important consideration in design and construction of timber buildings is moisture durability. This study characterized the hygrothermal performance of CLT panels with laboratory measurements at multiple scales, field measurements, and modeling. The CLT panels consisted of five layers, four with spruce-pine-fir lumber and one with Douglas-fir lumber. Laboratory characterization involved measurements on small specimens that included material from only one or two layers and large specimens that included all five layers of the CLT panel. Water absorption was measured with panel specimens partially immersed in water, and a new method was developed where panels were exposed to ponded water on the top surface. This configuration gave a higher rate of water uptake than the partial immersion test. The rate of drying was much slower when the wetted surface was covered with an impermeable membrane. Measured hygrothermal properties were implemented in a one-dimensional transient hygrothermal model. Simulation of water uptake indicated that vapor diffusion had a significant contribution in parallel with liquid transport. A simple approximation for liquid transport coefficients, with identical coefficients for suction and redistribution, was adequate for simulating panel-scale wetting and drying. Finally, hygrothermal simulation of a CLT roof assembly that had been monitored in a companion field study showed agreement in most cases within the sensor uncertainty. Although the hygrothermal properties are particular to the wood species and CLT panels investigated here, the modeling approach is broadly applicable.