In this paper, the solubility of chlorpropamide (CPA) in 14 solvents including 8 alcohols (ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, iso-butanol, n-pentanol, and isopentanol) and 6 acetate esters (ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, amyl acetate, and methyl propionate) at temperatures of 283.15 to 323.15 K and atmospheric pressure was determined using a laser method. The solubility as a function of temperature was regressed using modified Apelblat, Van’t Hoff, λh, Wilson, and nonrandom two-liquid (NRTL) models. On the basis of the experimental and the simulation results, the mixing properties of the solutions, that is, mixing Gibbs energy, enthalpy, and entropy, were estimated.