The early and accurately detection of brucellosis incidence change is of great importance for implementing brucellosis prevention strategic health planning. The present study investigated and compared the performance of the three data mining techniques, random forest (RF), support vector machine (SVM) and multivariate adaptive regression splines (MARSs), in time series modelling and predicting of monthly brucellosis data from 2005 (March/April) to 2017 (February/March) extracted from a national public health surveillance system in Hamadan located in west of Iran. The performances were compared based on the root mean square errors, mean absolute errors, determination coefficient (R²) and intraclass correlation coefficient criteria. Results indicated that the RF model outperformed the SVM and MARS models in modeling used data and it can be utilized successfully utilized to diagnose the behaviour of brucellosis over time. Further research with application of such novel time series models in practice provides the most appropriate method in the control and prevention of future outbreaks for the epidemiologist.