The Middle and Lower Reaches of the Yangtze River metallogenic belt (MLYMB) is one of the most important Fe‐Cu polymetallic belts in China. However, the mechanism and deep geodynamical process for the formation of this belt are still controversial. Here, we obtain the crustal and the uppermost mantle structures using ambient noise data from a dense seismic profile. A low velocity zone is revealed beneath the Moho of MLYMB, interpreted as the source of the deep mineralization materials. In addition, a low velocity layer (LVL) and a high velocity layer (HVL) are observed in the crust of the southern segment of the profile. The LVL is interpreted as a tectonic detachment layer between the upper and the lower crust, and the HVL is interpreted as the aggregation zone for mineralizing melts or crystallized magma chambers. Based on the observed velocity features, we propose a three‐stage model for the formation of ore deposits in MLYMB. Our model suggests that an upwelling of asthenosphere triggered by the delamination of a previously thickened lithosphere leads to the partial melting of upper mantle rocks, which eventually ponders under the Moho. The magma then infiltrates through the ductile lower crust and reaches a depth of ∼7–13 km, forming a minerals‐enriched magma chamber. Minerals‐rich hot fluids originating from the magma chamber continue to move upward along the pre‐existent faults and the minerals finally precipitate in dense veinlets when reaching shallow depths, forming the ore deposits in and around the MLYMB. Plain Language Summary: The formation of large‐scale mineral deposits is closely related to the lithosphere structure. The Middle and Lower Reaches of the Yangtze River metallogenic belt (MLYMB) is an ideal place to study the mineral system, as it is one of the most important Fe‐Cu polymetallic metallogenic belts in Eastern China and contains more than 200 ore deposits. Yet the mechanism and deep geodynamical process for the formation of this belt are still controversial. In this study, we construct a high‐resolution seismic model of the crust and the uppermost mantle using ambient noise data from a dense seismic profile. Our result reveals velocity features closely related to the metallogenic process in this region. Based on the observed velocity features, we propose a three‐stage model for the formation of the ore deposits in MLYMB, which is of great importance for the development of "mineral system" approaches to the exploration of minerals worldwide. Key Points: We obtain a fine Vs structure of the crust and uppermost mantle beneath the MLYMBWe observe velocity features closely related to the metallogenic process of MLYMBWe propose a three‐stage metallogenic process for the origin of the MLYMB [ABSTRACT FROM AUTHOR]