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Cleaning is an important unit operation in food processing for removal of fouling deposits to ensure not only optimal operability of process equipment but also product safety and quality. In modern large-scale processing plants, cleaning is commonly achieved by cleaning-in-place (CIP) operation, which, however, consumes large amounts of water, energy, and chemicals. Because of their unique interfacial physicochemical properties, this study incorporated microbubbles (MBs) into water as a novel cleaning agent for the prerinse step of CIP operation, aiming to enhance its cleaning efficiency. MB-infused water (MB water) was introduced into bench-top spinning disc apparatus to clean milk deposits fouled on a stainless-steel surface. A computational fluid dynamics model was built to predict the contact frequency of MBs with deposits under swirl flow and further identify the cleaning conditions that provided maximum MB–deposit contact. MB–deposit attachment was visualized by microscopic imaging. A series of cleaning experiments were conducted at 25–55 °C and a Reynolds number (Re) of 3380–5403, and incorporation of MBs into water with 1431 bubbles/mL proved effective in increasing the cleaning efficiency at 25 °C and a Re of 4392 and 5403 by 27 and 31%, respectively. However, increasing water temperature and decreasing Re and bubble density were found to make the effect of MBs on cleaning insignificant. The findings of this study can serve as the groundwork for developing an MB-assisted CIP system to improve the environmental performance of food manufacturing.