Cleaning strategies in restoration and conservation often involve the use of solvent mixtures, despite the fact that the interaction between these and the objects under treatment is not always well known. Binary solvent mixtures behave nonideally; that is, the properties are not directly proportional or related to the mixing ratio. This fact contradicts the trivialized solubility charts, for example, the Teas chart, known and applied in practical restoration. The description of the dissolving action of binary systems therefore requires additional information such as the solvation and solubilization mechanisms involved. The effects of binary solvent mixtures on oil and alkyd paints were systematically investigated, with particular focus on the swelling action and leaching of binding media components. In total, 75 binary mixtures made from the solvents n-hexane, toluene, chloroform, diethyl ether, acetone, and ethanol were experimentally applied to free paint films by immersion. The solvation was studied by application of the linear solvation energy relationship based on Catalan’s solvatochromic system. Extracted components were quantified gravimetrically and characterized with Fourier transform infrared spectroscopy, direct temperature-resolved mass spectrometry, and gas chromatography mass spectrometry. Selective solvation is observed both in oil and alkyd paints, but to a variable extent. The nonideal action of solvent mixtures, however, arises primarily from a lowering of the cavitation energy within the liquid by the formation of associates. This effect is thus a solute-independent process, which raises the entropy of mixing. As a consequence, many of the solvent mixtures tested had a far more detrimental effect on the paint films than the pure solvents.