Disorders of lipid metabolism are a common cause of coronary heart disease (CHD) and its comorbidities. In this study, ultra-performance liquid chromatography-high-resolution mass spectrometry in data-independent acquisition (DIA) mode was applied to collect abundant tandem mass spectrometry data, which provided valuable information for lipid annotation. For the lipid isomers that could not be completely separated by chromatography, parallel reaction monitoring (PRM) mode was used for quantification. A total of 223 plasma lipid metabolites were annotated, and 116 of them were identified for their fatty acyl chain composition and location. In addition, 152 plasma lipids in patients with CHD and its comorbidities were quantitatively analyzed. Multivariate statistical analysis and metabolic pathway analysis demonstrated that glycerophospholipid and sphingolipid metabolism deserved more attention for CHD. This study proposed a method combining DIA and PRM for high-throughput characterization of plasma lipids. The results also improved our understanding of metabolic disorders of CHD and its comorbidities, which can provide valuable suggestions for medical intervention.