Air-dried beef, a traditional dry fermented meat product in China, whose quality is largely influenced by processing conditions. In this study, contact ultrasound (CU) and infrared radiation (IR) were employed to enhance hot air drying (HAD), with an investigation into the mechanisms underlying improvements in quality and flavor. Samples subjected to CU and IR treatments during HAD (CU-IRD) demonstrated superior color (L* = 42.68, a* = 5.05, b* = −3.86) and tenderness (140.59 N) than HAD group, primarily attributed to reduced drying times and alterations in ultrastructure. Analyses utilizing SDS-PAGE and total volatile basic nitrogen (TVB-N) revealed that HAD and CU-HAD resulted in significant protein oxidation (197.85 mg TVB-N/kg and 202.23 mg TVB-N/kg, respectively), while IR treatments were associated with increased thermal degradation of proteins, producing lower molecular weight peptides. Compared with HAD group, the activities of certain lipases and proteases were enhanced by ultrasound and infrared treatments, leading to the release of greater amounts of free fatty acids and flavor amino acids. Furthermore, the thermal effects of infrared and the cavitation effects of ultrasound contributed to increased fat oxidation, amino acid Strecker degradation, and esterification reactions, thereby augmenting the diversity and concentration of volatile flavor compounds, including alkanes, ketones, aldehydes, and esters. These findings indicate that the synergistic application of CU and IR represents a promising strategy for enhancing the quality of air-dried beef.