We explore two principal areas of uncertainty associated with paleoclimate reconstructions from speleothem δ18O (δ18Ospel): potential non-stationarity in relationships between local climate and larger-scale atmospheric circulation, and routing of water through the karst aquifer. Using a δ18Ospel record from Turkey, the CSIRO Mk3L climate system model and the KarstFOR karst hydrology model, we confirm the stationarity of relationships between cool season precipitation and regional circulation dynamics associated with the North Sea-Caspian pattern since 1 ka. Stalagmite δ18O is predicted for the last 500 years, using precipitation and temperature output from the CSIRO Mk3L model and synthetic δ18O of precipitation as inputs for the KarstFOR model. Interannual variability in the δ18Ospel record is captured by KarstFOR, but we cannot reproduce the isotopically lighter conditions of the sixteenth to seventeenth centuries. We argue that forward models of paleoclimate proxies (such as KarstFOR) embedded within isotope-enabled general circulation models are now required.