Stable isotope composition of speleothems reflects the physicochemical condition of their formation environment such as the local temperature and the isotopic composition of surface precipitation, making them one of the best archives of terrestrial climate. However, quantitative reconstruction of paleo-temperature from speleothem isotope records is challenging, because most speleothems do not form in isotope equilibrium with the drip water. These disequilibrium isotope effects, often thought to arise from the rapid degassing of CO2 from a thin water film, vary among different speleothems and over time, and hinder the applications of many isotope thermometers in speleothems, including both the conventional carbonate-water oxygen isotope thermometer and the recently developed carbonate clumped isotope thermometer. Here we present an isotope-enabled reaction-diffusion model of speleothem formation (IsoCave), and use it to systematically examine the patterns and controls of the disequilibrium isotope effects in speleothems (δ13C, δ18O, Δ′17O, Δ47, Δ48 and Δ49) and explore their implications for isotope thermometry in speleothems.We show that prior calcite precipitation, cave air pCO2 and δ13CCO2exert the strongest controls on the disequilibrium isotope effects in speleothems, followed by cave temperature, water film thickness and water drip rate. Together, changes in these environment parameters explain the variations of disequilibrium isotope effects in natural speleothems. Our model reproduces the apparent temperature dependence of oxygen isotope compositions of speleothems compiled from multiple caves over a large temperature range, but highlights the challenges in the application of speoleothem-specific calibration of isotope thermometers due to the effects of non-temperature factors. Further, we show the disequilibrium effects in different isotope systems are highly correlated. The slopes of these correlations reflect mainly the kinetic isotope fractionations associated with HCO3− dehydration and dehydroxylation reactions, and remain relatively constant despite changes in environmental conditions especially for speleothems formed during the early evolution period of drip water. Based on these correlations, specifically the correlation between disequilibrium Δ47 and Δ48 effects, we propose a novel approach to quantitatively correct for disequilibrium isotope effects in speleothems and derive more accurate estimates of speleothem formation temperatures. Application of this coupled Δ47-Δ48 approach to synthetic speleothem isotope records reproduces the speleothem formation temperatures, suggesting new opportunities for quantitative paleo-temperature reconstruction based on speleothem isotope records.