Priming effects can influence the efficiency with which organic amendments sequester carbon in the soil. Yet, few soil models currently include priming effects. Those models that do are often based on operationally defined soil pools and implicitly allow only for positive priming effects. This limits the verification of model processes with experimental data and hinders the optimization of our carbon sequestration strategies. To address these shortcomings, we developed MiPrime, which offers a framework for the mechanistic modelling of organic amendment impacts on microbially mediated transformation of carbon fractions that are quantifiable through parsimonious soil extraction methods. MiPrime allows for assessment of organic amendment impacts on soil carbon dynamics, including priming effects, by simulating changes in mineralized, microbial biomass, dissolvable, hot water extractable and insoluble carbon fractions in soil exogenous (i.e. organic amendment-derived) and endogenous (i.e. soil) pools. After calibration of model parameters using Markov Chain Monte Carlo methods to incubation data of three types of isotopically labelled roadside grasses (a fresh grass product, a compost thereof, and a Bokashi-fermented product thereof), MiPrime was able to simulate changes in carbon fractions of the soil with a good degree of accuracy for five compositionally complex organic amendments, namely the three types of roadside grasses, as well as non-isotopically labelled wood chips and water weeds and reeds. Validation of the model results with experimental data demonstrates that changes in total carbon were very well predicted but that there is room for improvement in predicting mineralization rates and changes in dissolvable, hot water extractable and insoluble carbon fractions in the soil endogenous pool. MiPrime thus offers an initial step towards the mechanistic modelling of organic amendment impacts on measurable soil carbon fractions and can operate as a new tool for designing effective carbon sequestration strategies and understanding organic amendment impacts.