Shepstone eventually turned on the Zulus, as he felt he was undermined by Cetshwayo's skillful negotiations for land area and compromised by encroaching Boers, as well as the fact that the Boundary Commission established to examine the ownership of the land in question had dared to rule in favour of the Zulus.

He banished European missionaries from his land and may have incited other native African peoples to rebel against Boers in the Transvaal.

While this retreat presented an opportunity for a Zulu counterattack deep into Natal, Cetshwayo refused to mount such an attack; he intended to repulse the British offensive and secure a peace treaty.

However, Cetshwayo's translator, a Dutch trader he had imprisoned at the start of the war named Cornelius Vijn, gave warnings to Chelmsford of gathering Zulu forces during these negotiations.

This, along with his gentle and dignified manner, gave rise to public sympathy and the sentiment that he had been ill-used and shoddily treated by Bartle Frere and Lord Chelmsford.

By 1882, differences between two Zulu factions—pro-Cetshwayo uSuthus and three rival chiefs led by Zibhebhu—had erupted into a blood feud and civil war.

With the aid of Boer mercenaries, Chief Zibhebhu started a war contesting the succession, and on 22 July 1883, he attacked Cetshwayo's new kraal in Ulundi.

After pleas from the Resident Commissioner, Sir Melmoth Osborne, Cetshwayo moved to Eshowe, where he died a few months later on 8 February 1884, aged 57–60, presumably from a heart attack, although there are some theories that he may have been poisoned.

Cetshwayo's most prominent role in South African historiography is being the last king of the Zulu Kingdom, though it still exists.

In the short story A Municipal Report in Strictly Business by O. Henry (1910), the face of a key character is compared to that of "King Cettiwayo".

A character in the opera Leo, the Royal Cadet by Oscar Ferdinand Telgmann and George Frederick Cameron was named in his honour in 1889.

In the 1964 film Zulu, he was played by Mangosuthu Buthelezi, his maternal great-grandson and the future leader of the Inkatha Freedom Party.