Escherichia coli K12 cells suspended in apple cider were treated by manothermosonication (MTS, 400 kPa/59 °C), thermosonication (TS, 100 kPa/59 °C), and manosonication (MS, 400 kPa/55 °C) for up to 4 min. A 5-log reduction was achieved in 1.4 min by MTS, 3.8 min by TS, and 2.5 min by MS. The inactivation curves of the E. coli exhibited a fast initial reduction followed by a slow inactivation section. The Weibull, log-logistic, and biphasic linear models showed a good fit of the inactivation data. Quality analyses were conducted with raw apple cider (control), thermally-pasteurized (TP), and MTS-, TS-, and MS-treated cider samples over a 3-week period at refrigeration temperature. Titratable acidity and pH did not differ among any of the samples. During storage, the turbidity value of the control was the highest, followed by TP, TS, MTS and MS. All color parameters of the TP sample were significantly different from those receiving the other treatments. The control and sonicated samples showed similar color parameters during storage. In total, 97 aroma compounds were identified in the control, TS-, MS-, and MTS-treated cider samples, while 95 aroma compounds were found in the TP at Week 0. Among all the aroma compounds, 9 key ones were identified in all samples, including ethyl 2-methylbutanoate, butyl acetate, 1-butanol, ethyl hexanoate, 1-hexanol, butanoic acid, β-damascenone, hexanoic acid, and octanoic acid. The profiles of the key aroma compounds in all sonicated samples were more similar to the control than the TP sample at Weeks 0 and 3.