To overcome the problems of a long conventional drying time, low energy efficiency, and poor product quality, a segmented drying approach was developed for fresh wolfberry (Lycium barbarum) using a radio frequency (RF)-hot air drying process, which was investigated under different parameters of plate spacing (80, 90, 100 mm), vacuum degree (0.015, 0.025, 0.035 Mpa), and hot air temperature (50, 55, 60 °C). Analysis of the wolfberry’s drying characteristics, comprehensive quality, and microstructure indicated that: combined drying was faster and less time-consuming than natural drying or hot air drying, and components such as polysaccharides, ascorbic acid, and betaine in wolfberries were effectively retained. Based on the acceptable drying rate, stable temperature application, and avoidance of arcing effects, the optimal combined segmented drying parameters were determined to be as follows: a plate spacing of 90 mm, vacuum degree of 0.025 MPa, and air temperature of 55 °C. For the dried wolfberries under these conditions, the total drying time was 17 h and the berries had an improved comprehensive quality, the content of total soluble sugars was 0.62 g/g, total phenol was 10.01 mg/g, total flavonoids was 2.60 mg/g, VC was 3.18 mg/100 g, betaine was 3.48%, oxidation resistance represented by an inhibition rate was 66.14%, color was better, and rehydration rate was 48.56%. The microstructure was more regular because of the special dielectric heating characteristics of RF vacuuming. Despite the differing drying characteristics of individual materials, the overall RF-hot air combined drying process was found to achieve high-quality dehydration of wolfberries.