The Dolphin returned in 1766. Its circumnavigation of 22 months was the shortest up to that point. Upon his return Clerke published an account of encountering Patagonian giants, which the Dictionary of Canadian Biography attributed to his high spirits.
Clerke's last three voyages were all under the command of Captain James Cook.
Clerke started the first voyage aboard HM Bark Endeavour (1768–1771) as a master's mate. Cook promoted him to acting lieutenant in 1771. Clerke was HMS Resolution's second lieutenant on Cook's second voyage (1772–1775).
While ashore between Cook's 2nd and 3rd voyages Clerke agreed to serve time in the Fleet debtor's prison for a debt one of his brothers, Sir John Clerke, incurred. While in debtor's prison he was infected with the tuberculosis that eventually killed him.
Clerke continued the expedition's exploration of the Northern Pacific coast, searching for a navigable Northwest Passage. The expedition then proceeded to the Pacific coast of Siberia. James King, one of his subordinates, wrote that Clerke's illness had reduced him to skeletal thinness. Clerke died en route to Kamchatka from tuberculosis. Clerke was buried in Kamchatka on August 29, 1779.
Clerke's second in command, John Gore, took command and took the expedition home to Britain.