Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease characterized by hepatocellular lipid overload, inflammatory activation, and hepatic stellate cell (HSC)–mediated fibrogenesis. Human genetic studies have identified loss-of-function (LoF) variants in 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) that confer robust protection against advanced fibrosis and cirrhosis, establishing HSD17B13 as a critical modifier of MASH severity. However, the mechanisms linking HSD17B13 activity to fibrogenesis remain incompletely understood. Here, we demonstrate that both native and catalytically deficient HSD17B13 (mHSD) localize to lipid droplets (LDs) in human hepatocytes. Only catalytically active HSD17B13 enhances lipid storage and markedly upregulates the lipogenic transcriptional regulator carbohydrate-responsive element–binding protein (ChREBP). This HSD17B13–driven lipogenic program promotes activation of human LX2 stellate cells both in direct co-culture and upon exposure to hepatocyte-conditioned medium (CM). Screening of candidate signaling mediators revealed that transforming growth factor β-1 (TGFβ-1) is uniquely and robustly induced by HSD17B13 expression, whereas mHSD elicits minimal induction. Notably, siRNA-mediated TGFB1 knockdown or antibody neutralization of active TGFβ-1 effectively abrogates CM-induced LX2 activation and collagen synthesis. Collectively, these findings delineate an HSD17B13–TGFβ-1 signaling pathway that mechanistically couples hepatocellular lipid dysregulation to stellate cell-mediated fibrogenesis. This work reveals a dual metabolic and profibrotic role for HSD17B13 and underscores its therapeutic potential as a target for mitigating the transition from simple steatosis to steatohepatitis.