Shelf-life of pasteurized milk is limited by heat-stable proteases, which cause gelation and bitterness. Ultra-high temperature processing inactivates proteases, but detrimentally affects milk quality. An adjunct to pasteurization is sought to extend milk shelf-life, while maintaining sensory properties. In this study, we evaluated the effects of combined heat and ultrasound on the activity of Staphylococcus aureus protease and total plasmin, as well as the impact on sensory properties of milk and cream. Sonication at 133 µm (p.p) for 2.5 min decreased the enzyme activity by approximately 72% in pasteurized skim and whole milk and by 92% in commercial pasteurized reduced-fat milk. Viscosity of commercial pasteurized milk samples that were thermosonicated at 133 µm (p.p) for 2.5 min was not affected. However, off-aromas (cooked and plastic/rubbery) were observed in commercial pasteurized reduced-fat and whole milk treated with 133 µm (p.p) for 2.5 min. Thermosonication at 152 µm (p.p) for 3 min decreased the plasmin activity by about 81 to 94% in raw skim milk and by 96% in raw cream. Enzyme activity in most raw skim milk samples measured at the end of 4 weeks was one- to two-fold higher than that on day 0, whereas in most raw cream samples enzyme decreased with storage time. Descriptive analysis of odor attributes of raw skim milk and raw cream that were thermosonicated at 152 µm (p.p) for 3 min was conducted for up to 4 weeks with 8 trained panelists. No significant differences were observed between the intensities of offensive eggy and rubbery odor attributes of thermsonicated skim milk and pasteurized commercial skim milk and cream (p<0.05). Lightness (L*) values of raw skim milk and cream were not adversely affected by thermosonication. Thermosonication did not adversely affect the viscosity of skim milk and cream samples when measured over the 4-week storage period. Thermosonication decreased the fat globule size in both skim milk and cream and the homogenizing effect increased with increase in treatment time. Thermosonication at 133 and 152 µm (p.p) for 1 and 3 min completely destroyed coliforms and destroyed over 99% of the total aerobic bacteria. The total aerobic bacteria count of thermosonicated skim milk and cream samples were less than 20,000 CFU/mL on day 30. Because thermosonication did not induce off-aromas or viscosity changes, but inactivated microorganisms and protease enzymes, thermosonication may be an appropriate adjunct to pasteurization to extend milk shelf-life.