Non-damaging ultraviolet B (UV-B) light promotes photomorphogenic development and stress acclimation through UV-B-specific signal transduction in Arabidopsis . UV-B irradiation induces monomerization and nuclear translocation of the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8). However, it is not clear how the nuclear localization of UVR8 leads to changes in global gene expression. Here, we reveal that nuclear UVR8 governs UV-B-responsive transcriptional networks in concert with several previously known transcription factors, including ELONGATED HYPOCOTYL 5 (HY5) and PHYTOCHROME INTERACTING FACTOR 4 (PIF4). Based on the transcriptomic analysis, we identify MYB13 as a novel positive regulator in UV-B-induced cotyledon expansion and stress acclimation. MYB13 is UV-B inducible and is predominantly expressed in the cotyledons. Our results demonstrate that MYB13 protein functions as a transcription factor to regulate the expression of genes involved in auxin response and flavonoid biosynthesis through direct binding with their promoters. In addition, photoactivated UVR8 interacts with MYB13 in a UV-B-dependent manner and differentially modulates the affinity of MYB13 with its targets. Taken together, our results elucidate the cooperative function of the UV-B photoreceptor UVR8 with various transcription factors in the nucleus to orchestrate the expression of specific sets of downstream genes and, ultimately, mediate plant responses to UV-B light.