Weathering is an important surface process that can cause the disintegration or decomposition of rocks that differ from unweathered rocks in structure or composition. To study the mechanism of mineral transition and the variation of major and trace elements in the weathering process of shale, the field weathering profile of the Silurian Hanchiatien Formation shale in northern Sichuan, thin section identification, whole-rock X-ray diffraction, X-ray fluorescence spectroscopy, inductively coupled plasma mass spectrometry, and other methods were used. The mineral composition and major and trace elements of different degrees of weathering of the rock samples were studied. The results show that the calcite and feldspar contents in the weathered samples noticeably decreased compared with the unweathered samples. Secondary minerals such as gypsum and clay were formed. According to the mass transfer coefficients of major and trace elements, it was concluded that Mg, Ca, Fe, Mn, Sr, and U were depleted. At the same time, Pb, Zn, Cu, Rb, and Cs were enriched simultaneously due to the weathering process. The content of rare earth elements increased in the regolith and resulted from absorption by clay minerals formed during the weathering process. According to the chemical alteration index (CIA=69.51~76.21), it can be judged that the weathering profile belongs to a moderate weathering degree. The A-CN-K diagram shows that the profile has reached the weak-to-moderate chemical weathering stage, the initial Ca and Na removal stage. According to the ratio variation diagram of Si/Al, Ca/Al, Mg/Al, Na/Al, K/Al, and P/Al in the vertical section and the element Pearson correlation analysis of samples, it can be found that calcite, apatite, and other minerals have undergone different degrees of decomposition. Secondary minerals such as iron-manganese oxides and illite are formed, and the elements occurring in the minerals also migrate. Therefore, the study of the coupling of mineral transition and element activity in weathering profiles is of great significance for revealing the weathering process and mechanism of shale.