Apricot (Prunus armeniaca L.) is an important fruit crop that is widely planted throughout the world. But drought affects both yield and quality of apricot. In order to study the effects of long-term drought on the molecular and physiological mechanisms of apricot, we used transcriptome sequencing and measured physiological indices. First, 322 million high-quality clean reads were obtained, and 74,892 unigenes were generated for the transcriptome. Among the assembled unigenes, 18,671 simple sequence repeats (SSRs) and 5581 differentially expressed genes (DEGs) were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs revealed that starch and sucrose metabolism, plant-pathogen interaction and plant hormone signal transduction pathways are enriched. Additionally, we used quantitative real-time PCR (qRT-PCR) to confirm the RNA-seq results with 11 drought-related DEGs. Second, through the physiological analysis of apricot leaves under constant drought stress, and the results show the internal microstructure of apricot leaves changed to withstand drought stress. At the same time, plants exposed to long-term drought stress showed higher degree of membrane damage, which reduced photosynthesis in the damaged leaves. Our findings enrich the genome resources for apricot and refine our understanding of the molecular and physiological mechanisms of drought response in this fruit crop, providing insights into drought adaptation of the apricot.