Highly Pathogenic Avian Influenza (HPAI) is of major importance for human and animal health because of high morbidity and mortality in poultry and the potential for transmission of this zoonotic pathogen to humans. Knowledge of HPAI epidemiology in avian populations and practical information on the temporal and spatial spread of the disease after introduction into a country is important in order to enhance the capacity of predicting and managing epidemics to minimize the negative impacts on human and animal health. Using data reported to the World Organisation for Animal Health between 2005 and 2017 by 199 countries for 14,129 outbreaks in poultry, we used a spatial and time-series analysis to determine that: 1) During the last 12 years, there were two major global peaks in the number of countries affected by HPAI with 23% and 26% of countries affected in 2006 and 2016. 2) Based on the seasonality analysis, spread is the lowest in September, begins to rise in October, and peaks in February. 3) The median distance HPAI outbreaks spread from the index outbreak was 111 km, while the median apparent rate of spread of outbreaks was 1.9 km/day. 4) In 39% of HPAI events, the disease did not spread beyond the index outbreak and the median maximum spread from the index outbreak per event was 45 km. 5) The distance HPAI outbreaks spread from the index outbreak was significantly negatively correlated with the number of outbreaks during the same time period, indicating that the spread of HPAI was lower during global panzootics than during periods of low transmission. These findings are of major importance for veterinary services to design and implement surveillance measures for improving preparedness to minimize the impacts of this disease.