The discovery and rise of graphene were historically enabled by its similar to 10% optical contrast on specialized substrates like oxide-capped silicon. However, substantially lower contrast is obtained on transparent substrates. Moreover, it remains difficult to visualize nanoscale defects in graphene, including voids, cracks, wrinkles, and multilayers, on most device substrates. We report the use of interference reflection microscopy (IRM), a facile, label-free optical microscopy method originated in cell biology, to directly visualize graphene on transparent inorganic and polymer substrates at 30-40% image contrast per graphene layer. Our noninvasive approach overcomes typical challenges associated with transparent substrates, including insulating and rough surfaces, enables unambiguous identification of local graphene layer numbers and reveals nanoscale structures and defects with outstanding contrast and throughput. We thus demonstrate in situ monitoring of nanoscale defects in graphene, including the generation of nanocracks under uniaxial strain, at up to 4X video rate.