Prior to the arrival of the first Europeans it is believed that the Adnyamathanha people had already been exposed to contagious diseases such as small pox. Many people believe that the Macassan traders, who sailed from the Indonesian islands to northern Australia, were the first to introduce diseases to the Australian continent.

The first Europeans to travel through Adnyamathanha lands were Edward John Eyre and his exploration party in 1840. Such was the shock of seeing Europeans for the first time that Adnyamathanha people first thought they were white skinned spirits. Many Aborigines hid and watched the group at a distance as they were very cautious. In his report of this exploration, Eyre wrote that he encountered little conflict with the Adnyamathanha people but there were incidents that caused tensions. For example when the exploration party were running out of water one of his overseers kidnapped an Adnyamathanha woman to question her about local water sources. As a result, the camp was surrounded by Aboriginal people who "..repeatedly exhibited signs of defiance, such as throwing dust into the air, shouting and threatening with their weapons." (Eyre, E.J. in Education Department of South Australia, 1992: 128)

After a few years, European settlers started to move into the Flinders Ranges and they bought with them odd animals and goods which were alien to the Adnyamathanha. They were warned beforehand of the Europeans by message sticks from other Aboriginal groups, so many went into hiding. Adnyamathanha people observed the goods which the Europeans had bought with them and saw how useful these goods were. Eventually the barrier of caution between the Aborigines and the Europeans broke down.

After a few years, European settlers started to move into the Flinders Ranges and they bought with them odd animals and goods which were alien to the Adnyamathanha. They were warned beforehand of the Europeans by message sticks from other Aboriginal groups, so many went into hiding. Adnyamathanha people observed the goods which the Europeans had bought with them and saw how useful these goods were. Eventually the barrier of caution between the Aborigines and the Europeans broke down.

The settlement of land in South Australia was first planned by private individuals in Britain who came together with the intention of selling the land to other settlers. For this to work, they had to have the support of the British government to make it legal. Finally, in 1834 an act was passed which established South Australia as a colony. This act "declared Aboriginal lands to be 'waste and unoccupied'." (Education Department of South Australia, 1992: 134) With this act, British citizens were able to buy any land they wanted. After the act was passed, English humanitarian groups protested that the rights of the Aborigines should be protected. This protest was a success and in 1835, Lord Glenelg proposed a scheme so that the Aborigines would at least be compensated for their land. This proposal made the Board of Colonisation Commissioners uneasy because they thought that the sale of lands would stop and result in economic failure. "A protector was appointed to protect Aboriginal people against violence, to provide sustenance, shelter, education and Christian instruction, but the protector was given no control over land sale." (Education Department of South Australia, 1992: 134) After the act was passed, a set of Government regulations, called Letters Patent, were made stating how the Act would be applied in the colonisation of South Australia.