Overpressure is widespread in the southern margin of the Junggar Basin, northwestern China. Pressure measurements in drillstem tests and repeated formation tests and estimates from wire-line logs indicate contrasting overpressure values between permeable sandstones and adjacent low-permeability mudrocks. In addition, excess pressure differs among anticlines with similar depth, lithologies, and geologic age, indicating significant lateral changes of overpressure. Major factors controlling overpressure generation and distribution include rapid sediment deposition, pressure compartmentalization by thick mudrocks, tectonic stress, faulting, and folding. Clay transformation and hydrocarbon generation are believed to be insignificant in overpressure generation in the southern Junggar Basin. Numerical modeling of pressure generation and evolution suggests that faulting and stratal tilting associated with folding are the most significant factors in the overpressure generation of a permeable sandstone. The extremely high overpressure (pressure coefficient up to 2.43) may have been caused by hydraulic adjustment within permeable sandstones associated with structural deformation caused by post-Miocene intense tectonic activities.