Mulberry ( spp.) is an economically significant plant in the production of silk through feeding leaves to silkworm larvae. Traditional silkworm rearing is heavily labor-intensive, particularly in leaf collection, which leads to low efficiency and impedes the development of sericulture. Here, to assess the feasibility and effectiveness of a novel low-pruning mulberry cultivar, ZJ1, in the silkworm rearing industry, a comprehensive investigation integrating physiological, proteomic, and metabolomic analyses was conducted in comparison with the traditionally high-pruning cultivar, N14. The low-pruning mulberry variety ZJ1 exhibited a notable increase in annual leaf yield of 43.94%, along with a significant enrichment of serine and isoleucine contents, in contrast to those of the high-pruning variety N14. Through iTRAQ proteomics and LC-MS/MS metabolomics analyses, a total of 561 reduced and 803 increased differentially expressed proteins (DEPs), as well as 332 differential expressed metabolites (DEMs) in positive ions and 192 DEMs in negative ions, were identified in the ZJ1 group relative to the N14 group, respectively. The observed features in amino acid profiles and the enrichment of the sucrose-related metabolic pathway provided interesting insights for future endeavors in mulberry variety improvement and the optimization of silkworm diet formulations. Collectively, the low-pruning cultivar ZJ1, characterized by its rapid growth, high leaf productivity, and suitability for mechanized operations, is expected to be an efficient substitute in improving the future sericultural industry, especially in urbanized and industrialized regions.