The South Island, larger, more mountainous, and very thinly settled by Maoris, presented problems which took longer to solve. In the 1840s, while Company agents were pressing north from Wellington, others were searching for farm land for the luckless Nelson settlers or else looking at the east coast for fresh sites. Frederick Tuckett, in 1841, revealed the Waimea Plain; the next year S. J. Cotterill reported good land to the east, around the Wairau, Awatere, and Clarence Rivers. The Wairau Affray of 1843 diverted attention briefly to the west, where it was rumoured a great fertile plain existed. Efforts to penetrate to the south-west of Nelson culminated in the great journeys of Thomas Brunner, especially that of 1846–48, one of the most arduous explorations in the whole story. Taking in all some 560 days, Brunner went down the Buller River to the sea, past the Wanganui River, Okarito and the Waiho River, as far south as Tititira Point. He then came back up the coast to the Grey River, noting the presence of coal, and returned to Motueka via the Inangahua and Buller Rivers. On a previous journey he had learned from the local Maoris that they had access to Canterbury across the mountains.

Similar information was gathered from Canterbury Maoris in 1844 by Edward Shortland during a coastal trip from Otago to the Deans' (q.v.) station at Riccarton, near the future site of Christchurch. In the early 1840s Shortland and Tuckett explored around the Waikouaiti, Taieri, Otago Harbour and Clutha River regions; Tuckett in 1844 reported in favour of a settlement at Otago. Charles Kettle was perhaps the first European to see Central Otago; while further north W. Heaphy was the first to journey up the Canterbury coast north of Kaiapoi, reaching in 1845 the Waiau River. W. B. D. Mantell, while engaged upon land purchase for the Government in 1848, travelled from Kaiapoi to Dunedin, much further inland than any of his forerunners. In 1849 and 1850, W. J. W. Hamilton, a surveyor sent by the New Zealand Company to join the Admiralty survey vessel, Acheron, opened up a good deal of the interior. He found good grazing land between Kaiapoi and the Waiau River, and, in a whale boat, charted much of the coast from Cook Strait to Banks Peninsula. In 1850, while the Acheron was in the Foveaux Strait region, he went up the Oreti and Aparima Rivers, and overland from the Bluff to Dunedin.

In the 1850s the most significant pressure is applied by sheep; graziers sought routes and grassland between Nelson and Canterbury, from the Canterbury coast to the mountains, and in the Otago interior. In the 1860s this continuous impulse is complemented by the more hectic appetite for gold; graziers and prospectors opened up all but the most remote parts of the South Island, leaving little but the glaciers and the high peaks for the more disinterested explorer.

After the foundation of Canterbury, Nelson sheepowners were keen to find a stock route south so that they could sell sheep to the new runholders. In 1850 Frederick Weld and C. Wilkinson went up the Awatere River and across the Barefell Pass to the Acheron River, a tributary of the Clarence. Thinking they had found a route to North Canterbury, they sent 700 sheep that way the next year, but they had to be abandoned. In 1850 W. M. Mitchell and E. Dashwood had, using the Waihopai, Awatere, Acheron and Clarence Rivers, and crossing the range to North Canterbury, found a way, which was not, however, a suitable stock route. E. J. Lee and Edward Jollie were the first to find such a route. In 1852 they took 1,800 sheep up to Awatere, and Jollie detected a pass through to the Hanmer plains. Subsequently many parties took sheep and cattle along this lengthy, difficult, but usable route – from Tophouse down the Wairau, up the Awatere, over Barefell Pass, and through Jollies Pass to North Canterbury. Weld, in 1855, shortened the route by opening the Tarndale route between Tophouse and the Acheron.