This study investigated the individual and combined effects of ultraviolet A (UV-A) and far-red (FR) light irradiation on the biomass, phytochemical accumulation, and antioxidant capacity of two lettuce cultivars in an artificial light plant factory. UV-A supplementation yielded a smaller leaf area and reduced biomass and nitrate content. In contrast, it improved the chlorophyll, soluble protein, soluble sugar, vitamin C, flavonoid, polyphenol, and anthocyanin contents and the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging rate. FR irradiation resulted in a larger leaf area, whereas the lettuce biomass remained unchanged. Irradiation with both UV-A and FR light exhibited the most remarkable effect on leaf expansion and biomass, but reduced the phytochemical contents. A significant interaction between the cultivar and supplemented light was observed for most plant parameters.