TEAD1 induces cardiac fibroblast remodeling through the BRD4/Wnt4 pathway. Cardiac fibroblasts (CFs) are crucial for collagen deposition and remodeling, and are closely associated with heart failure (HF). TEAD1, a transcription factor, is essential for heart development and homeostasis. However, its role in cardiac remodeling remains unclear. Transcriptomic analysis showed increased TEAD1 expression in mice with heart remodeling. CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout in CFs and myofibroblasts reduced TAC-induced cardiac remodeling. Mechanistically, TEAD1 interacts with BRD4 to activate the Wnt4 promoter, promoting fibroblast-to-myofibroblast transition. TEAD1 inhibition with VT103 ameliorated cardiac remodeling. These findings suggest TEAD1 is a key regulator of pathological cardiac remodeling via the BRD4/Wnt4 pathway.TEAD1 induces cardiac fibroblast remodeling through the BRD4/Wnt4 pathway. Cardiac fibroblasts (CFs) are crucial for collagen deposition and remodeling, and are closely associated with heart failure (HF). TEAD1, a transcription factor, is essential for heart development and homeostasis. However, its role in cardiac remodeling remains unclear. Transcriptomic analysis showed increased TEAD1 expression in mice with heart remodeling. CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout in CFs and myofibroblasts reduced TAC-induced cardiac remodeling. Mechanistically, TEAD1 interacts with BRD4 to activate the Wnt4 promoter, promoting fibroblast-to-myofibroblast transition. TEAD1 inhibition with VT103 ameliorated cardiac remodeling. These findings suggest TEAD1 is a key regulator of pathological cardiac remodeling via the BRD4/Wnt4 pathway.