Metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic lipid accumulation, inflammation, and fibrosis, is a major risk factor of cardiovascular disease. MASH increases the risk of myocardial infarction and stroke by two- to three-fold and frequently co-occurs with obesity and diabetes. As the final reversible stage before cirrhosis, MASH lacks effective early treatments, and the temporal cellular mechanisms driving disease progression remain unclear. We analyzed a mouse MASH model induced by a choline-low, high-fat, high-sucrose diet at weeks 1, 4, 8, and 12 using histologic, physiologic, and single-cell transcriptomic profiles. MASH-fed mice developed progressive liver pathology, with hepatomegaly and dysfunction by week 4 and steatosis and fibrosis by week 8, mirroring human disease. Single-cell transcriptomics revealed extensive remodeling of hepatic and immune compartments, including an early surge of Cd11b+ myeloid cells at week 1. T cell infiltration increased at weeks 8-12 alongside hepatocyte stress and fibrotic signaling. Secretome and MacSpectrum analyses identified a temporal shift from early metabolic responders (Lgals3, Mif, Smdt3) at weeks 1-2 to inflammatory mediators (Cxcl10, Tnf, Il10) at weeks 8-12, highlighting temporally coordinated immune-parenchymal signaling during MASH progression.