A series of experimental simulations were conducted to study the effects of supercritical CO2-water on the dissolution of illite under different burial depth conditions (1,000, 1,500, and 2,000 m). In addition, the mineral composition, crystalline structure, and fluid composition were analyzed. The results indicate that illite dissolution is controlled by solid-liquid diffusion and surface chemical reactions. The elements that undergo metathesis are more easily released than the original fixed elements in the crystal lattice, and the interlayer cations are released more easily than octahedral and tetrahedral ions. At deeper burial depths, the percentages of dissolved ions increase. After the reaction, the crystallinity of illite decreases, the proportion of amorphous material increases, and the morphology changes with damage to the lattice. Meanwhile, the dissolution of illite can contribute to the generation of diaspore and siderite.