In 1848 Petherick left the Egyptian service and established himself at El Obeid, the capital of Kordofan, as a trader, dealing largely in gum arabic. He was at the same time made British consular agent for the Sudan. In 1853 he removed to Khartum and became an ivory trader. He travelled extensively in the Bahr-el-Ghazal region, then almost unknown, exploring the Jur River, Yalo and other affluents of the Bahr el Ghazal river.
In 1858 he penetrated to the Niam-Niam country. His additions to the knowledge of natural history were considerable, among his discoveries being the Mrs Gray's waterbuck and the Shoebill. Petherick returned to England in 1859 where he made the acquaintance of JH Speke, then arranging for his expedition to discover the source of the Nile. While in England Petherick married, and published an account of his travels.
He returned to the Sudan in 1861, accompanied by his wife and with the rank of consul. He was entrusted with a mission by the Royal Geographical Society to convey to Gondokoro relief stores for Captains Speke and Grant. Petherick got boats to Gondokoro in 1862, but Speke and Grant had not arrived. Having arranged for a native force to proceed south to get in touch with the absentees, a task successfully accomplished, Mr and Mrs Petherick undertook another journey in the Bahr-el-Ghazal, making important collections of plants and fishes. They regained Gondokoro (where one of their boats with stores was already stationed) in February 1863, four days after the arrival of Speke and Grant, who had meantime accepted the hospitality of Mr (afterwards Sir) Samuel Baker.
The charge that Petherick failed to meet his engagement to those travellers is unsubstantiated. A further charge that Petherick had countenanced and even taken part in the slave trade was subsequently shown to have no foundation (Petherick in fact had endeavoured to stop the traffic), but it led Earl Russell, then secretary for foreign affairs, to abolish the British consulate at Khartoum in 1864.
In 1865 the Pethericks returned to England, and in 1869 published Travels in Central Africa and Explorations of the Western Nile Tributaries, in which book are set out the details of the Speke controversy. Petherick died in London, on the 15th of July 1882.