We report that for monolayer and few-layer graphene on common silicon and glass substrates, acidic solutions induce fast, spontaneous generation of solution-enclosing blisters/bubbles. Using interference reflection microscopy, we monitor the blister-generating process in situ and show that at pH < ∼2, nanoscale to micrometer-sized graphene blisters, up to ∼100 nm in height, are universally generated with high surface coverages on hydrophilic, but not hydrophobic, surfaces. The spontaneously generated blisters are highly dynamic, with growth, merging, and reconfiguration occurring at second-to-minute time scales. Moreover, we show that in this dynamic system, graphene behaves as a semipermeable membrane that allows the relatively free passing of water, impeded passing of the NaCl solute, and no passing of large dye molecules. Consequently, the blister volumes can be fast and reversibly modulated by the solution osmotic pressure.