During the process of flue-curing and processing, leaves from cash crops such as tea and tobacco frequently undergo a phenomenon of browning, leading to reduced quality and significant economic losses. Despite a variety of approaches developed to suppress browning, little is known about the role that flue-curing of postharvest leaves with stems plays in delaying browning. This study investigated the impact of leaf-with-stem (LWS) flue-curing on the browning of tobacco and its underlying mechanisms. Physiological results indicated that LWS flue-curing effectively delayed browning by enhancing antioxidant capacity and maintaining reactive oxygen species (ROS) levels during the yellowing stage. Comprehensive transcriptome and metabolome analyses showed that LWS flue-curing significantly influenced various metabolic pathways. Specifically, 196, 218, and 402 metabolites, and 65, 131, and 718 genes exhibited significant changes at the 38 °C, 40 °C, and 42 °C stages, respectively, inhibiting membrane lipid degradation and enhancing the supply of reducing hydrogen through the oxidative pentose-phosphate pathway. Additionally, hormone signaling pathways were found to be associated with LWS flue-curing. These findings highlight the complex interplay of metabolic pathways and signaling networks in attenuating browning, providing valuable insights for minimizing postharvest leaf browning during flue-curing and processing.