In this study we examined isocyanate crosslinking reactions at the film-air (F-A) and film-substrate (F-S) interfaces of waterborne two-component (2K) urethanes as a function of depth and relative humidity (RH) using attenuated total reflectance (ATR) FTIR spectroscopy. Analysis of water/isocyanate reactions revealed urea formation which further interacts with water via H-bonding. Quantitative analysis of isocyanate consumption showed that the rates of film formation for waterborne polyurethanes are faster than equivalent solvent-borne polyurethanes. These studies showed that isocyanate consumption increases at high relative humidities. Examination of isocyanate consumption as a function of depth from the F-A and F-S interfaces showed that the isocyanate concentration increases when going from 0.65 to 1.14 µm.