The metabolic disorders are becoming an epidemic disease endangering public health in countries. Environmental factors are mainly reason for the growth of metabolic disorders. Previous research suggests that DNA methylation is a potential mechanism. Recently, it has been reported that DNA hydroxymethylation is also a stable marker of epigenetic reprogramming. Hence, the study aims to investigate whether DNA hydroxymehylation mediates early-life environmental stress-evoked metabolic disorder in adulthood. Mice were orally administered with arsenic (As), an environmental stressor, throughout pregnancy. We show that early-life As exposure induces glucose intolerance and hepatic lipid accumulation in adulthood. Early-life As exposure alters epigenetic reprogramming and expression of lipid metabolism-related genes including β-oxidation-specific genes in adulthood. Of interest, early-life As exposure alters epigenetic reprogramming of hepatic lipid metabolism partially through reducing DNA hydroxymethylation modification of β-oxidation-related genes in developing liver. Mechanistically, early-life As exposure suppresses ten-eleven translocation (TET) activity through downregulating isocitrate dehydrogenases (Idh) and reducing alpha-ketoglutarate (α-KG) content in the developing liver. In addition, early-life As exposure inhibits TET1 binding to CpG-rich fragments of β-oxidation-related genes in developing liver. This study provide novel evidence that early-life environmental stress leads to later life metabolic disorders by altering hepatic DNA hydroxymethylation reprogramming. Display omitted •Early-life As exposure alone induces hepatic lipid accumulation in adulthood.•Early-life As exposure causes epigenetic reprogramming of hepatic β-oxidative-related genes in adulthood.•As-altered epigenetic reprogramming of hepatic β-oxidation-related genes begins with changes in 5hmC at fetal period.•Early-life As exposure inhibits TET activity by reducing α-KG contents in the developing liver.•Early-life As exposure suppresses TET1 binding to CpG-rich sites of β-oxidative-related genes in the developing liver.