There is currently no evidence that the intervertebral discs (IVDs) can respond positively to exercise in humans. Some authors have argued that IVD metabolism in humans is too slow to respond anabolically to exercise within the human lifespan. Here we show that chronic running exercise in men and women is associated with better IVD composition (hydration and proteoglycan content) and with IVD hypertrophy. Via quantitative assessment of physical activity we further find that accelerations at fast walking and slow running (2 m/s), but not high-impact tasks, lower intensity walking or static positions, correlated to positive IVD characteristics. These findings represent the first evidence in humans that exercise can be beneficial for the IVD and provide support for the notion that specific exercise protocols may improve IVD material properties in the spine. We anticipate that our findings will be a starting point to better define exercise protocols and physical activity profiles for IVD anabolism in humans.