Identifying cold-related genes can provide insights into the cold adaptation mechanism of weeping forsythia. In this study, we compared the changes in gene expressions and physiological and biochemical indices under short-term cold stimulation with the changes in gene sequences under a long-term heterogeneous environment to investigate the cold adaptation mechanism in weeping forsythia. The data of adaptive gene sequence changes, e.g., single nucleotide polymorphisms, were obtained from previous landscape genomics studies. The physiological and biochemical indicators and transcriptome results showed that weeping forsythia initiated a series of programs, including increasing cell osmotic pressures, scavenging ROS, activating the defense mechanism that crosses with pathogen infection, and upregulating CBF/DREB1 transcription factor 1, to cope with short-term cold stress. A reanalysis of landscape genomic data suggested that weeping forsythia responded to long-term heterogeneous cold stress by the differentiation of genes related to synthesis of aromatic substances and adenosine triphosphate. Our results supported the hypothesis that the adaptation mechanisms of species to short-term environmental stimulation and long-term stress in heterogeneous environments are different. The differences in cold tolerance among populations are not necessarily obtained by changing cold-responsive gene sequences. This study provides new insights into the cold adaptation mechanisms of plants.