Similar to compositional evolution of sandstone modes and detrital heavy minerals from different profiles in the Kuqa Depression, Northwest China, major element analysis of whole sandstones from the same profiles shows four discontinuous depositional interfaces or periods, respectively corresponding to Lower TriassicMiddle Triassic, Upper JurassicLower Cretaceous, Lower CretaceousPaleogene and MiocenePliocene, and indicates five-phase evolution during Mesozoic-Cenozoic: (1) From the first to fifth phase, a depositional suite changes from maroon and coarse clastic, through grey-dark grey and fine, red and coarse, red-mottled, interlayered by gypsum, to brown and coarse clastic assemblages, accompanying detrital component evolution in unstable-stable-unstable-very unstable-very unstable assemblages. It is indicated that carbonate and complex detritus gradually dominate in sandstones in post-Late Jurassic, with rapid reduction of compositional maturity. (2) For major element geochemical parameters of whole sandstones, CaO and +MgO contents show a change sequence in high-low-high-higher-highest values, with rapid increasing in post-Late Jurassic. (3) Contra some aggregative indicators for weathering indexes of sandstone detrital component, Al2O3/(CaO+Na2O) and ln(Q/(L+CE)), show a change sequence in low-high-low-lower-lowest ratios, with rapid decreasing in post-Late Jurassic. It is found that sandstone samples of the first, second and later three phases may be distinguished from the A-CN-K and A-CNK-FM diagrams respectively. Therefore, in the Kuqa Depression-Tianshan, the most important discontinuous depositional interface recording paleotectonic and paleoclimatic transition occurred in Early TriassicMiddle Triassic and Late JurassicEarly Cretaceous, respectively, and, however, tectonic differentiations of basin-range system finally result in distinct depositional systems but similar detrital weathering indexes across the Lower CretaceousPaleogene and Miocene Pliocene interfaces, respectively.