Segment drying is the major physiological disorder that deteriorates fruit quality and results in loss of flavor and edible value of fruits, including mainly granulation-type segment drying and collapse-type segment drying. Few research had been focused on the latter. Using Tarocco blood orange upon collapse-type segment drying as study material, widely targeted metabolomics was used to analysis primary metabolite and metabolic pathway changes of collapse-type segment drying, amino acid content analysis, enzyme activity assay, and gene expression analysis were utilized to elucidate the mechanism underlying the rapid deterioration of citric acid during segment drying. The results showed that a total of 193 differentially primary metabolites were identified in juice vesicles upon segment drying, citric acid content significantly decreased by 53.1%, the metabolites relative to the acetyl-CoA synthesis pathway (such as serine, linoleic acid and other lipids) increased significantly, the gene expression of lipid metabolism was up-regulated upon segment drying, while the expression of gene CsACLs encoding ATP-citrate lyase remained unchanged. Glutamine synthetase activity increased by 75.3% in vesicles upon segment drying. γ-Aminobutyric acid content remained unchanged, glutamine decarboxylase activity was not changed, the expression of gene CsGADs encoding glutamine decarboxylase was down-regulated upon segment drying. In conclusion, the acetyl coenzyme A synthesis pathway was the main pathway for the rapid degradation of citric acid in vesicles of blood orange during collapse-type segment drying. The results aimed to provide a reference for clarifying the mechanism of collapse-type segment drying in citrus fruit.