Lethal ventricular tachyarrhythmia (LVTA) is the most prevalent electrophysiological underpinning of sudden cardiac death (SCD), a condition that occurs in response to multiple pathophysiological abnormalities. The aim of this study was to identify common lipid features of LVTA that were induced by distinct pathophysiological conditions, thereby facilitating the discovery of novel SCD therapeutic targets. Two rat LVTA-SCD models were established to mimic myocardial infarction (MI) and myocardial ion channel diseases. Myocardial and serum specimens were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics. The lipid profiles of the myocardial and serum specimens were similar between the models. Eleven myocardial lipid classes were altered, including downregulations of: cardiolipin, ceramide, phosphatidylinositol, phosphatidylethanolamine, triacylglycerol, diacylglycerol, phosphatidylglycerol, lysophosphatidylethanolamine and phosphatidylserine, and upregulations of: lysophosphatidylcholine and phosphatidic acid. Serum concentrations of triacylglycerol, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol were also altered. Alterations of lipids in paired myocardia and sera were closely correlated. Cardiolipin 70:5, cardiolipin 74:9 and ceramide d34:2 were tested as potential biomarkers of LVTA. The results indicate that there are common LVTA lipid profiles induced by MI and myocardial ion channel diseases, potentially offering novel LVTA-SCD therapeutic targets.