The Miocene SQ21.0 sequence of the Zhujiang Formation in the Baiyun Depression, Pearl River Mouth Basin, developed large-scale deep-water fan sandstone stratigraphic reservoirs related to a mixed-source deep-water canyon system. Based on the 3-dimensional high-resolution sequence stratigraphy method constrained by drilling data, this study details the morphology, filling evolution, and main controlling factors of a mixed-source deep-water canyon system of clastic and carbonate rocks in the SQ21.0 sequence during the Miocene in the Baiyun Depression, Pearl River Mouth Basin. Our findings show that the mixed-source canyon system extends >150 km from the continental shelf break to the southern slope and is distributed in a SN direction in the eastern area of the Baiyun Depression, which presents a characteristic three-segment pattern, such as the head of the upper slope canyon system, Baiyun East Depression on the middle slope, and Yunli Low Uplift Liwan Depression on the lower slope. The profile topology has evolved from a V-shaped upper slope to a U-W-shaped middle and lower slope, and in the plane, it has evolved from multiple divergent canyons into a large canyon system. The development and distribution of the mixed-source canyon system of the Zhujiang Formation were controlled by the evolution of the dual source of the Paleo-Pearl River Delta-Dongsha Uplift platform, relative sea-level changes, shelf breaks, and restricted slope landforms. During the early forced regression of relative sea-level decline, a sand-rich canyon channel system supplied by the coastline system of the Paleo-Pearl River Delta and Dongsha Uplift developed, with significant erosion to the shelf-break-outer shelf and restricted slope change areas. Conversely, during transgression to the highstand period of relative sea level rise, with the retreat of the Paleo-Pearl River Delta source and rapid growth of reefs on the Dongsha Uplift platform, a large-scale canyon channel system supplied by argillaceous/carbonate detritus developed, with intense incision erosion occurring in the upper-middle section of the strongly restricted steep slope filled with relatively rich mud or lime debris. Canyon channel systems were filled with mud or lime debris, with a near-NS-oriented distribution, cutting across the nose-shaped structural belts and underlying early deep-water sand fan bodies in the near EW direction, forming large-scale stratigraphic trap groups which serve as key breakthrough areas for the recent exploration of stratigraphic traps in Baiyun deep-water areas.