AbstractHigh pressure has become a powerful platform for creating and controlling novel states of matter, including high temperature (T_c) superconductivity. However, the emergent phenomena generally disappear as high pressure is removed and cloud prospects for future applications. Here, from a distinguishing perspective, FeSe_1−xS_x is reported as 2D van der Waals materials with extraordinary high‐T_c at ambient pressure, where the superconductivity is boosted by extreme “chemical pressure” inside the materials. Superior to external high pressure, isovalent S substitution in FeSe leads to a much greater compression rate within the superconducting iron‐chalcogenide layer, which guarantees an unabridged superconducting dome that peaked at 37.5 K. Density functional theory calculations reveal that the decreased lattice and structural parameters contribute together for the shift of Fe 3d_x2−y2 orbital, which creates a new hole‐pocket at the Fermi level that intimately correlated with the enhanced superconductivity. This study demonstrates the design of materials with optimized superconductivity by introducing chemical pressure.