The Hindu Kush–Himalaya (HKH) region is an essential component of the global ecosystem, playing a crucial role in global climate regulation and ecological balance. This study employed a remote sensing ecological index (RSEI) with Geodetector to evaluate the eco-environmental quality and its driving factors within the HKH region. Results revealed a statistically significant upward trend (p < 0.05) in eco-environmental quality across the HKH region during 2001–2023, with the average RSEI value increasing by 23.9%. Areas classified as the Good/Excellent grades (RSEI > 0.6) expanded by ~12%, while areas at the Very Poor grade (RSEI ≤ 0.2) shrunk by ~20%. However, areas classified as the Poor (0.2 < RSEI ≤ 0.4) and Moderate (0.4 < RSEI ≤ 0.6) grades increased by ~11% and ~5%, respectively. This resulted in ~11% of the total area degraded across the HKH. Spatially, the highest ecological quality occurred in the southern Himalayan countries (sub-region R2), followed by China’s Tibetan Plateau (sub-region R3), while the northwestern HKH region (sub-region R3) exhibited the lowest ecological quality. Notably, the sub-region R3 and eastern sub-region R1 had the most pronounced improvement. Precipitation and land cover type were the dominant driving factors, exhibiting nonlinear enhancement effects in their interactions, whereas topographic factors (e.g., elevation) had limited but stable influences. These findings elucidate the spatiotemporal dynamics of HKH’s eco-environmental quality and underscore the combined effects of climatic and geomorphic factors, offering a scientific basis for targeted conservation and sustainable development strategies.