Wood plays a vital role in human life. It is important to study the thickening mechanism of tree branches and explore the mechanism of wood formation. Elm (Ulmus pumila) is a strong essential wood, and it is widely used in cabinets, sculptures, and ship making. In the present study, phenotypic and comparative transcriptomic analyses were performed in U. pumila fast- (UGu17 and UZuantian) and slow-growing cultivars (U81-07 and U82-39). Phenotypic observation showed that the thickness of secondary xylem of 2-year-old fast-growing branches was greater compared with slow-growing cultivars. A total of 9367 (up = 4363, down = 5004), 7159 (3413/3746), 7436 (3566/3870), and 5707 (2719/2988) differentially expressed genes (DEGs) were identified between fast- and slow-growing cultivars. Moreover, GO and KEGG enrichment analyses predicted that many pathways were involved in vascular development and transcriptional regulation in elm, such as “plant-type secondary cell wall biogenesis”, “cell wall thickening”, and “phenylpropanoid biosynthesis”. NAC domain transcriptional factors (TFs) and their master regulators (VND1/MYB26), cellulose synthase catalytic subunits (CESAs) (such as IRX5/IRX3/IRX1), xylan synthesis, and secondary wall thickness (such as IRX9/IRX10/IRX8) were supposed to function in the thickening mechanism of elm branches. Our results indicated that the general phenylpropanoid pathway (such as PAL/C4H/4CL) and lignin metabolism (such as HCL/CSE/CCoAOMT/CCR/F5H) had vital functions in the growth of elm branches. Our transcriptome data were consistent with molecular results for branch thickening in elm cultivars.