Artemisiae argyi Folium (AAF) is a popular herbal medicine that is always employed in moxa sticks and by oral dosage in clinical use. Less attention has been paid to nonvolatile compounds as active compounds, such as phenolic acids and flavonoids. In this study, we focused on the variation rule of phenolic acids and flavonoids in the various transformations of Artemisiae argyi Folium. Using the established ultra-performance liquid chromatography (UPLC) method with an excellent methodology under “spider-web” mode, six phenolic acids and three flavonoids were simultaneously quantified in fresh and drying Artemisiae argyi Folium as well as in moxa wool and residue. Some interesting phenomena about the variation rule of phenolic acids and flavonoids were uncovered. First, a sharp increase was observed in the detected compounds’ content as the moisture gradually decreased, when fresh Artemisiae argyi Folium was exposed to sunlight and ambient or high temperature. Nevertheless, the increased phenolic acids were subjected to high temperature, leading to obvious degradation under oven-drying (60 °C and 80 °C). Second, a wide content distribution was revealed for the detected compounds in Artemisiae argyi Folium from different habitats, especially rutin, caffeic acid, chlorogenic acid, jaceosidin, eupatilin, and cryptochlorogenic acid. Third, accompanied by the elevated ratio of Artemisiae argyi Folium/moxa wool, the detected compounds conspicuously decreased in moxa wool and the correspondingly removed powder as residue. Importantly, a greater variation was found in moxa wool. Our findings contribute to the optimization of the drying process, the quality evaluation of the various transformations of Artemisiae argyi Folium, and the distinctive characterization of moxa wool produced at different ratios of Artemisiae argyi Folium/moxa wool.