High pathogenicity avian influenza (HPAI) has become a major focus point worldwide due to its zoonotic potential and economic effects resulting from trade restrictions and high mortality rates in poultry. Key ostrich producing provinces of South Africa have experienced three H5N2 HPAI outbreaks (2004, 2006 and 2011) and one H5N8 HPAI (2017) outbreak over the past two decades.The Klein Karoo region in the Western Cape Province, a province with a largely Mediterranean climate, is the predominant ostrich producing region in the country. Understanding the epidemiology of HPAI in ostrich producing areas is an essential first step in developing effective and efficient control measures. This study investigated the spatiotemporal patterns associated with the 2011 (H5N2) and 2017 (H5N8) HPAI outbreaks in the key ostrich producing areas of South Africa. Six hundred and nine and 340 active ostrich farms/holdings were subjected to surveillance during 2011 and 2017 respectively, with over 70 % of these farms located within five local municipalities of the study area. Forty-two and fifty-one farms were affected in the 2011 and 2017 outbreaks respectively. Both HPAI outbreaks occurred predominantly in areas of high ostrich farm density. However, the temporal occurrence, spatial and directional distributions of the outbreaks were different. The 2011 outbreak occurred earlier in the South African autumn months with a predominantly contiguous and stationary distribution, whilst the 2017 outbreak onset was during the winter with a more expansive multidirectional spatial distribution. Results suggest potential dissimilarities in the important risk factors for introduction and possible mode of spread. The 2011 outbreak pattern resembled an outbreak characterised by point introductions with the risk of introduction possibly being linked to high ostrich farm density and common management and husbandry practices in the ostrich industry. In contrast, the 2017 outbreak appeared to have a more propagating mode of transmission. The findings highlight epidemiological features of HPAI outbreak occurrence within ostrich populations that could be used to inform surveillance and control measures including targeted surveillance within high-risk spatial clusters. The study emphasizes the importance of both; implementation of a multi-pronged approach to HPAI control and the need for constant evaluation of the interaction of the host, environment and agent with each outbreak, in order to strengthen disease control.