Fluidized roasting is an efficient method to promote vanadium extraction from V-bearing mica in shale. In this study, the transformation behavior of V-bearing sericite during fluidized roasting was explored by combining experimental detections and density functional theory (DFT) calculations. TG-MS, XRD, FTIR, and SEM-EDS were used to investigate the characteristics of the roasted sericite samples. The crystal parameters of V-bearing sericite were calculated with Materials Studio. The results showed that dehydroxylation was the main reaction during roasting, which occurred between 650 °C and 960 °C. After being roasted at 900 °C for 2 h, hydroxyls were completely removed. The calculation results show that −OH was removed between the metal ions in the sericite O-layer, which turned the hexa-coordinate of V³⁺, Al³⁺, and Fe³⁺ into pentacoordinate. Through electronic rearrangement, the bond lengths between two ions connected by −OH were shortened from 0.18~0.20 nm to 0.17 nm. However, some chemical bonds were grown, which indicates that they are weaker and easier to transform. In addition, twisted six-membered rings were formed with obvious angle changes on the (0 0 1) surface. Furthermore, Mulliken’s overlap populations of some V-O, Al-O, and Fe-O were decreased. Therefore, dehydroxylation is a determining factor in the destruction of sericite crystals during fluidized roasting, which also promotes vanadium release from shale.