The Pliocene offers insights into future climate, with near-modern atmospheric pCO2 and global mean surface temperature estimated to be 3–4°C above pre-industrial. However, the hydrological response differs between future global warming and early Pliocene climate model simulations. This discrepancy results from the use of reduced meridional and zonal sea surface temperature (SST) gradients, based on foraminiferal Mg/Ca and Alkenone proxy evidence, to force the early Pliocene simulation. Subsequent, SST reconstructions based on the organic proxy TEX86, have found warmer temperatures in the warm pool, bringing the magnitude of the gradient reductions into dispute. We design an independent test of Pliocene SST scenarios and their hydrological cycle “fingerprints.” We use an isotope-enabled General Circulation Model, iCAM5, to model the distribution of water isotopes in precipitation in response to four climatological SST and sea-ice fields representing modern, abrupt 4 × CO2, late Pliocene and early Pliocene climates. We conduct a proxy-model comparison with all the available precipitation isotope proxy data, and we identify target regions that carry precipitation isotopic fingerprints of SST gradients as priorities for additional proxy reconstructions. We identify two regions with distinct precipitation isotope (D/H) fingerprints resulting from reduced SST gradients: the Maritime Continent (D-enriched due to reduced convective rainfall) and the Sahel (wetter, more deep convection, D-depleted). The proxy-model comparison using available plant wax reconstructions, mostly from Africa, is promising but inconclusive. Additional proxy reconstructions are needed in both target regions and in much of the world for significant tests of SST scenarios and dynamical linkages to the hydrological cycle.