Originally a Dutch farmer of Graaff-Reinet, Cape Colony, and a descendant from one of thc earliest Dutch settlers in South Africa, he left his home in the Great Pretorius Trek, and by way of what is now the Orange Free State crossed the Drakensberg into Natal, where he arrived in November 1838, at a time when the emigrants there were without a recognized leader. Pretorius was at once chosen commandant-general and speedily collected a force to avenge the massacre of Piet Relief and his party, who had been treacherously killed by the Zulu king Dingane the previous February.
Pretorius's force was attacked on the 16 December (" Dingaan's Day ") by over 10,000 Zulus, who were beaten off with a loss of 3000 men in what became known as the Battle of Blood River. In January 1840 Pretorius with a commando of 400 burghers helped Mpande in his revolt against his brother Dingane and was the leader of the Natal Boers in their opposition to the British. In 1842 he besieged the small British garrison at Durban, but retreated to Maritzburg on the arrival of reinforcements under Colonel (subsequently Sir) Josias Cloete and afterwards exerted his influence with the Boers in favor of coming to terms with the British.
He remained in Natal as a British subject, and in 1847 was chosen by the Dutch farmers there to lay before the governor of Cape Colony the grievances under which they labored owing to the constant immigration of natives, to whom locations were assigned to the detriment of Boer claims. Pretorius went to Grahams Town, where Sir Henry Pottinger (the governor) then was; but Sir Henry refused to see him or receive any communication from him. Pretorius returned to Natal determined to abandon his farm and once more trek beyond the British dominions.
With a considerable following he was preparing to cross the Drakensberg when Sir Harry Smith, newly appointed governor of the Cape, reached the emigrants' camp on the Tugela (Jan. 1848). Sir Harry promised the farmers protection from the natives and persuaded many of the party to remain, but Pretorius departed, and on the proclamation of British sovereignty up to the Vaal fixed his residence in the Magalisberg, north of that river. He was chosen by the burghers living on both banks of the Vaal as their commandant-general. At the request of the Boers at Winburg Pretorius crossed the Vaal in July and led the anti-British party in their "war of freedom," occupying Bloemfontein on the 20th of the same month. In August he was defeated at Boomplaats by Sir Harry Smith and thereupon retreated north of the Vaal, where he became leader of one of the largest of the parties into which the trans-Vaal Boers were divided, and commandant-general of Potchefstroom and Rustenburg, his principal rival being Commandant-General A. H. Potgieter.
In 1851 he was asked by the Boer malcontents in the Orange River Sovereignty and by the Basuto chief Moshesh to come to their aid, and he announced his intention of crossing the Vaal to "restore order" in the Sovereignty. His object, however, was rather to obtain from the British an acknowledgment of the independence of the Transvaal Boers. The British cabinet having decided on a policy of abandonment, the proposal of Pretorius was entertained. A reward of 2000 which had been offered for his apprehension after the Boomplaats fight, was withdrawn, Pretorius met the British commissioners at a farm near the Sand River, and with them concluded the convention (17 January, 1852) by which the independence of the Transvaal Boers was recognized by Great Britain.
Pretorius recrossed the Vaal and at Rustenburg on the 16th of March was reconciled to Potgieter, the followers of both leaders approving the convention, though the Potgieter party was not represented at the Sand River. In the same year Pretorius paid a visit to Durban with the object of opening up trade between Natal and the new republic. He also in 1852 attempted to close the road to the interior through Bechuanaland and sent a commando to the western border against Sechele. During this expedition David Livingstone's house at Kolobeng was looted.
Pretorius died at his home at Magalisberg in July 1853. He is described by Theal as "the ablest leader and most perfect representative of the Emigrant Farmers." In 1855 a new district and a new town were formed out of the Potchefstroom and Rustenburg districts and named Pretoria in honor of the late commandant-general.