Highly pathogenic Avian influenza (HPAI) is a fatal zoonotic disease that damages the poultry industry and endangers human lives via exposure to the pathogen. A risk assessment model that precisely predicts high-risk groups and occurrence of HPAI infection is essential for effective biosecurity measures that minimize the socioeconomic losses of massive outbreaks. However, the conventional risk prediction approaches have difficulty incorporating the broad range of factors associated with HPAI infections at poultry holdings. Therefore, it is difficult to accommodate the complexity of the dynamic transmission mechanisms and generate risk estimation on a real-time basis. We proposed a continuous risk prediction framework for HPAI occurrences that used machine learning algorithms (MLAs). This integrated environmental, on-farm biosecurity, meteorological, vehicle movement tracking, and HPAI wild bird surveillance data to improve accuracy and timeliness. This framework consisted of the generation of 1,788 predictors from six types of data and reconstructed them with an outcome variable into a data mart based on a temporal assumption (i.e., infected period and day-ahead forecasting); ii) training of the predictors with the temporally rearranged outcome variable that corresponded to HPAI H5N6 infected state at each individual farm on daily basis during the 2016-17 HPAI epidemic using three different MLAs (Random Forest, Gradient Boosting Machine [GBM]) and eXtreme Gradient Boosting); iii) predicting the daily risk of HPAI infection during the 2017-18 HPAI epidemic using the pre-trained MLA models for each farm across the country.The models predicted the high risk to 8-10 out of 19 infected premises during the infected period in advance. The GBM MLAs outperformed the seven day forecasting of HPAI prediction at individual poultry holdings, with an area under the curve (AUC) of receiver operating characteristic of 0.88. Therefore, this approach enhances the flexibility and timing of interventions against HPAI outbreaks at poultry farms.