On 1 January 1908, Nimrod sailed from Lyttleton Harbour, beginning the British Imperial Antarctic Expedition. The trip's goal was to land a party of between nine and twelve men, who would then proceed to the South Pole, at the site of Discovery's landing in February 1908 and to return to retrieve them in 1909. The party was to break into three groups, two of which would explore King Edward VII Land and Mount Melbourne. The third and main team was to reach the geographic South Pole.

To conserve coal, the ship was towed 2,700 kilometres (1,678 mi) by Konya to the Antarctic ice. Shackleton arranged for the expense to be split between the New Zealand government and the Union Steamship Company. Upon arrival on 14 January 1908, at the Antarctic Circle, the crew found that Discovery's base camp was inaccessible. Accordingly, Shackleton's base camp was built on Ross Island at Cape Royds, about 40 kilometres (25 mi) north of the planned site. The party was in high spirits despite difficult conditions and the sickness of crew members. During this trip, Shackleton acquired his nickname, "the Boss", due to his leadership abilities, which focused on camaraderie and admiration.

The South Pole Party (left to right): Wild, Shackleton, Marshall and Adams

The team was unable to attain its goal of reaching the South Pole because team-member Frank Wild was almost killed when a pony fell into a crevasse, injuring him and depriving the party of rations. Indeed, they were desperate for food, and Shackleton decided that it would be impossible for the entire team to return alive if they continued. However, Shackleton and his companions reached 88° 23' S, a point only 180 kilometres (112 mi) from the Pole, which would stand as the "Farthest South" record until Amundsen reached the Pole in 1911 (followed shortly by Robert Scott's ill-fated Terra Nova Expedition which Shackleton had assisted by managing the ordering of provisions). The expedition's accomplishments also included the first ascent of Mount Erebus, an expedition to the approximate location of the Magnetic South Pole by Edgeworth David, Douglas Mawson, and Alistair MacKay (16 January 1909), and the discovery of the Beardmore Glacier passage (named after Shackleton's patron). The group was the first to cross the Trans-Antarctic mountain range and to set foot on the South Polar Plateau.

Shackleton's party subsisted on half-rations during the return march, and at one point the Boss gave the one biscuit allotted for the day to Frank Wild. With conditions dire, the group returned to base camp on 28 February 1909, and found a letter stating that Nimrod had sailed two days earlier. In response, the men burnt the camp to attract the departing ship's attention. The ploy succeeded, and by 1 a.m. on 4 March 1909, the whole party boarded for home.

Shackleton returned to the United Kingdom as a hero and was knighted. Soon after, he published a book about Nimrod's expedition titled The Heart of the Antarctic. Regarding the failure to reach the South Pole, Shackleton remarked to his wife: "Better a live donkey than a dead lion."

Ernest Shackleton in a publicity photo taken before the 1907–09 Nimrod Antarctic expedition