The open ocean nitrogen cycle is being altered by increases in anthropogenic atmospheric nitrogen deposition and climate change. How the nitrogen cycle responds will determine long-term trends in net primary production (NPP) in the nitrogen-limited low latitude ocean, but is poorly constrained by uncertainty in how the source-sink balance will evolve. Here we show that intensifying nitrogen limitation of phytoplankton, associated with near-term reductions in NPP, causes detectable declines in nitrogen isotopes (δ N) and constitutes the primary perturbation of the 21 century nitrogen cycle. Model experiments show that ~75% of the low latitude twilight zone develops anomalously low δ N by 2060, predominantly due to the effects of climate change that alter ocean circulation, with implications for the nitrogen source-sink balance. Our results highlight that δ N changes in the low latitude twilight zone may provide a useful constraint on emerging changes to nitrogen limitation and NPP over the 21 century.