An urgent challenge posed by climate change in warm grapevine-growing areas is accelerated ripening, which leads to rapid sugar accumulation while phenolics and aroma traits lag behind. Techniques that enable selectively delaying the sugar accumulation process without affecting the accumulation of secondary metabolites are essential. This study aimed to evaluate the effects of apical-to-cluster defoliation, manually applied in 2019 at the onset of veraison (D1) or 20 days later (D2), which removed about 30–40% of the pending total leaf area without altering the cluster microclimate compared with a non-defoliated control (C). Ripening trends, vegetative growth, yield components, and the final grape and wine composition, as well as wine sensorial attributes, were assessed. Although both treatments significantly lowered the final leaf area-to-yield ratio (0.80–0.90 m2/kg) compared with the 1.35 m2/kg recorded in the C vines, only D1 reduced the final total soluble solids (TSS) at harvest (2 °Brix less than C). However, the total anthocyanins were similarly limited, and titratable acidity (TA) did not differ from the C vines. The D1 wine was deemed similar to that made from control plants. Conversely, D2 failed to delay ripening, yet the D2 wine was deemed superior in terms of olfactory intensity, body, fruitiness, balance, and overall preference. Although the study was conducted over a single season, the results are robust enough to conclude that the timing of defoliation—i.e., the level of TSS concurrently reached by the C treatment—is crucial to achieving specific effects. Early defoliation appears valid for postponing ripening into a cooler period, making it quite interesting in warm–hot areas with a very long growing season; a much later defoliation, likely due to the interaction between mean canopy age and more light filtering from above the cluster zone, can elevate the quality of and appreciation for the final wine.