Rejuvenation of previously intruded silicic magma is an important process leading to effusive rhyolite, which is the most common product of volcanism at calderas with protracted histories of eruption and unrest such as Yellowstone caldera (Wyoming), Long Valley caldera (California), and Valles caldera (New Mexico) in the United States. Although orders of magnitude smaller in volume than rare caldera-forming supereruptions, these relatively frequent effusions of rhyolite are comparable to the largest eruptions of the 20th century, and pose a considerable volcanic hazard. However, the physical pathway from rejuvenation to eruption of silicic magma is unclear, particularly because the time between reheating of a subvolcanic intrusion and eruption is poorly quantified. This study uses nanometer-scale trace element diffusion in sanidine crystals to reveal that rejuvenation of a near-solidus or subsolidus silicic intrusion occurred in ∼10 mo or less following a protracted period (220 k.y.) of volcanic repose, and resulted in effusion of ∼3 km3 of high-silica rhyolite lava at the onset of Yellowstone’s last volcanic interval. The future renewal of effusive silicic volcanism at Yellowstone will likely require a comparable energetic intrusion of magma that remelts the shallow subvolcanic reservoir and generates eruptible rhyolite on month to annual time scales.