<p>The Tibetan Plateau is bounded by the Altyn Tagh left-lateral strike-slip fault system in the northwest, unlike the common thrust fault-bounded margins in the south or east. Quantifying surface denudation rate along this enigmatic margin is important for understanding tectonic-geomorphic evolution and deep dynamic processes at margins of the Tibetan Plateau. In this study, we collected modern river sand samples from 29 drainage basins along the eastern section of the Altyn Tagh fault zone and analyzed the concentrations of terrestrial <i>in-situ</i> cosmogenic nuclides ²⁶Al and ¹⁰Be. The ²⁶Al-¹⁰Be paired-nuclide method is effective in verifying the assumptions of steady-state denudation and short-term sediment transportation time in these basins, thereby ensuring the reliability of derived denudation rates. We found that ¹⁰Be-derived basin-wide denudation rates range from 15 to 610 mm kyr ⁻¹. Denudation rates are notably enhanced in locations with structural complexities that allow enhanced vertical uplift along this strike-slip fault system, such as restraining double bends and kinematic transition zones of fault junctions, and that the local topography becomes significantly steeper. This finding indicates that local tectonic uplift is the dominant factor governing topographic relief, as well as the intensity and spatial distribution of surface denudation. Basin-wide denudation rates exhibit a non-linear positive correlation with slope gradient, topographic relief, and channel steepness index (<i>k</i>_<i>sn</i>), suggesting that topographic indexes constitute robust proxies for estimating denudation rates in this region. Conversely, no discernible correlation was detected between denudation rates and rainfall or vegetation indices. Moreover, the spatial heterogeneity in rock type and thus erodibility exert non-negligible effects on surface denudation and landscape evolution, particularly in areas where tectonic uplift is less dominant. Our study provides for the first time millennial basin-wide denudation rates and their spatial distribution patterns along the northwestern margin of the Tibetan Plateau, and reveals the interplay between surface denudation and tectonic deformation along the Altyn Tagh fault. The results thereby fill an important knowledge gap in understanding surface processes across the poorly-understood plateau’s northwestern margin.</p>