Following Shaka's assassination by Dingane (28 September 1828) and Dingane's removal by Mpande (1839–40), the Zulu nation was fraught with uncertainty over the succession to the throne: Mpande however had legitimate sons. Succession of the Zulu monarchy was based on the first-born son of the great wife. However, in order to maintain his hold on the throne, a Zulu king quite often married his great wife late in life, or assigned the position to an existing wife late on.

Cetshwayo was born to the Zulu prince Mpande and his wife Ngqumbazi in 1826 at Mpande's homestead, emLambongwenya, in South-east Zululand. At the time, the Zulu nation was ruled by Mpande's brother Dingane. Cetshwayo's name means 'the Slandered One' possibly referring to a rumour over his legitimacy spread by Dingane. Although Dingane had eliminated all of his other brothers, Mpande was allowed to live: he had produced two sons thus ensuring a continuation of the royal line. Neither Dingane, or Shaka his predecessor, had produced offspring.

Mpande had announced his heir at an unusually early stage – even taking the step of introducing his son, Cetshwayo, to the Boer Volksraad at Pietermaritzburg in 1839. (The Boers took a nick out of Cetshwayo's ear to aid identification in later life – in a similar fashion to the tagging of cattle.) The Boers were aiding Mpande in his offensive against Dingane, and the provision of an heir gave him more credibility for continued good relations between Boers and the Zulu nation.

However, as Mpande aged, he became worried that Cetshwayo was gaining too much influence. Accordingly, Mpande encouraged Cetshwayo's brother Mbuyazi with the possibility of being made heir. This was perhaps justified, since in the resultant civil war (1856) Cetshwayo retained a considerable following amongst Mpande's izikhulu (council of elders); despite Mpande's outspoken support for Mbuyazi.

Drought and famine hit the Zulu nation in the summer of 1852–3 and various factions looked towards civil war as an opportunity to gain cattle. As the situation worsened, Mpande made more of his support for Mbuyazi. In November 1856 Mpande granted Mbuyazi a large tract of land in south-east Zululand; at the same time he refused to meet with Cetshwayo to discuss the succession question. Conflict became inevitable when Mbuyazi and his supporters, the iziGqoza, moved to their lands just north of the Thukela River, clearing the area of Cetshwayo's supporters.

Cetswayo mobilised his forces, known as the uSuthu, against Mbuyazi, and the two sides met at the Thukela, near the border with Natal. Colonial traders in the area, worried by the impending conflict, sent word to Natal. John Dunn, an administrative assistant to the Natal Border Agent rushed north with 35 Frontier Policemen and a hundred African hunters. John Dunn's force (known as iziNqobo, the Crushers) moved to 'negotiate' between Cetswayo and Mbuyazi, but motivated by personal gain he offered the services of his heavily armed force to Mbuyazi.