Red yeast rice is a nutraceutical fermented product used worldwide for the symptomatic relief of dyslipidemia and cardiovascular disease. However, the fermentation-induced lipid transformation from rice to red yeast rice remains unclear. Herein, an ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry method was developed for the comprehensive lipid analysis during fermentation. A total of 246 lipids fall in 21 subclasses were annotated in rice and red yeast rice, including 37 lysophospholipids, 14 phospholipids, 29 diglycerides, 114 triglycerides and fatty acid (15 species), ceramide (12 species), hexosylceramide (3 species), sitosterol ester (2 species), monogalactosyldiacylglycerol (2 species), digalactosyldiacylglycerol (2 species), monogalactosylmonoacylglycerol (8 species), digalactosylmonoacylglycerol (5 species), coenzyme Q (1 species), acyl hexosyl campesterol ester (1 species), and acylcarnitine (1 species). Results showed that lipid profiles changed, and new lipid species emerged. Notably, 18 medium- and long-chain triacylglycerols and triacylglycerols with short-chains were tentatively identified. These triacylglycerols also show the effects of body fat accumulation reduction, and hypolipidemic and hypoglycemic activities. Furthermore, lipid species that were profoundly changed were quantified, and the dynamic changes were investigated. This study clarified the molecular species and compositional changes in fermented rice from lipid aspect.