Ultrasonic (US) treatment was combined with pH shifting (pHS) and mild thermal (40 °C) (T40) treatment (US/T40/pHS) to improve the solubility of potato protein. The effects of the ultrasonication frequency, ultrasonication time, and incorporation sequence on the solubility of potato protein were investigated. The results showed that online US/T40/pHS treatment resulted in higher solubility of potato protein and enhanced free amino group release during in vitro digestion. The solubility of potato protein treated with online US/T40/pHS at a mono-frequency of 40 kHz for 15 min increased by 1.73 times compared with the control (p < 0.05). The digestibility rate increased by 16.0% and 30.8% during gastric and intestinal digestion, respectively, compared with the control (p < 0.05). It was demonstrated that online US/T40/pHS treatment significantly changed the secondary and tertiary structures of potato protein according to the results of circular dichroism and internal fluorescence. SDS-PAGE, particle size, and atomic force microscopy (AFM) showed that structural changes led to the formation of large soluble aggregates. The results suggested that the improvement in the solubility and digestibility of potato protein treated with online US/T40/pHS may be due to the formation of large soluble aggregates, which are more hydrophilic and sensitive to digestive enzymes.