Leaf senescence, the final stage of leaf development, is crucial for plant fitness as it enhances nutrient reutilization, supporting reproductive success and overall plant adaptation. Understanding its molecular and genetic regulation is essential to improve crop resilience and productivity, particularly in the face of global climate change. This review explores the significant contributions of natural genetic diversity to our understanding of leaf senescence, focusing on insights from model plants and major crops. We discuss the physiological and adaptive significance of senescence in plant development, environmental adaptation, and agricultural productivity. The review emphasizes the importance of natural genetic variation, including studies on natural accessions, landraces, cultivars, and artificial recombinant lines to unravel the genetic basis of senescence. Various approaches, from quantitative trait loci mapping to genome-wide association analysis and in planta functional analysis, have advanced our knowledge of senescence regulation. Current studies focusing on key regulatory genes and pathways underlying natural senescence, identified from natural or recombinant accession and cultivar populations, are highlighted. We also address the adaptive implications of abiotic and biotic stress factors triggering senescence and the genetic mechanisms underlying these responses. Finally, we discuss the challenges in translating these genetic insights into crop improvement. We propose future research directions, such as expanding studies on under-researched crops, investigating multiple stress combinations, and utilizing advanced technologies, including multiomics and gene editing, to harness natural genetic diversity for crop resilience.