Essential oil components (EOCs) have limited water solubility and are used at much higher concentrations in complex food matrices than in growth media to inhibit pathogens. However, the correlation between solubility and activity has not been studied. The objective of this work was to characterize the solubility of EOCs in solvents and milk and correlate solubility with antilisterial activity. The solubilities of four EOCs, thymol, carvacrol, eugenol, and trans-cinnamaldehyde, in water was significantly increased in the presence of 5% (vol/vol) ethanol. In milk, the solubility of EOCs was lower than in water, with lower solubility in higher-fat milk. EOCs applied to milk as stock solutions (in 95% aqueous ethanol) enabled quicker dissolution and higher solubility in milk serum than other methods of mixing, such as end to end, and greater reductions of Listeria monocytogenes Scott A after 0 and 24 h. When the EOC concentration detected in milk serum was above the minimum bactericidal concentration, complete inhibition of L. monocytogenes in tryptic soy broth resulted. Therefore, the antilisterial properties in milk could be correlated with the solubility by comparison to the minimum inhibitory or bactericidal concentrations of EOCs. While the EOCs applied using ethanol generally had solubility and activity characteristics superior to those of other mixing methods, ethanol is not used to a great extent in nonfermented foods. Therefore, mixing methods without an organic solvent may be more readily adaptable to enhancing the distribution of EOCs in complex food systems.