In the present work, the solubility of cannabidiol (CBD) is reported as a function of temperature (253.1–310.1 K) in four pure solvents: n-pentane, n-hexane, n-heptane, and iso-octane. Experimental data were obtained under a local pressure of 74 kPa by an isothermal method using an in situ filter to sample only the homogeneous liquid phase. The samples were analyzed by gravimetry and gas chromatography coupled with a flame ionization detector (GC-FID). A thermal analysis of the CBD by way of differential scanning calorimetry (DSC) was also carried out in order to determine its melting point and enthalpy of fusion. The solid–liquid equilibrium was theoretically studied using the Wilson equation, the nonrandom two-liquid (NRTL), and the UNIQUAC activity coefficient models in order to obtain a predictive model for CBD solubility. It was found that the melting point and the enthalpy of fusion for CBD were 341.4 ± 0.4 K and 21 ± 3 kJ mol–1, respectively. The mole fraction solubility of CBD was 2.44 × 10–3 at 253.1 K and 2.15 × 10–1 at 301.1 K in n-pentane, 2.22 × 10–3 at 253.1 K and 3.75 × 10–1 at 309.1 K in n-hexane, 2.43 × 10–3 at 254.1 K and 3.73 × 10–1 at 310.1 K in n-heptane, and 1.36 × 10–3 at 253.1 K and 2.61 × 10–1 at 309.6 K in iso-octane. Finally, the Wilson model was found to be the model that best reproduces the experimental data.