The first lease was taken up by G. Heinzmann in 1876, and the early venture aimed squarely at the British Indian Army, which needed sound horses for service on the North-West Frontier, in what is now Pakistan. The traditional owners of this country are the Mirning people, whose lands stretched across the Nullarbor and into South Australia long before any lease was pegged. Over the following decades the station changed hands and names many times. In 1888 the Madura Squatting and Investment Company floated to raise capital and take over the leasehold and surrounding blocks, finding the place carrying just 800 merino ewes and a few horses. By 1898 the Ponton brothers and John Sharp held it, when it was known as Clifton Downs Station.

The land tested everyone who tried to hold it. A rabbit plague swept west through the district in 1901, with millions of animals reported between Eucla and the Nullarbor. Artesian bores were sunk deep, one pumping 37,000 imperial gallons a day from 2,200 feet to keep stock alive. Drought and flood took turns. In 1948 some 400 cattle died for lack of feed, the survivors driven away in search of water. Yet water also drew people in: one bore that had flowed continuously for 28 years became a warm bathing place for travellers crossing the desert, and a trap for the several hundred brumbies running wild on the station in 1933.

Isolation made every emergency a matter of life and death. In 1935 the station manager, W. O'Donovan, fell dangerously ill, and Goldfields Airways flew a doctor in aboard a new Fox Moth and carried him to Kalgoorlie. He died the next day of an internal haemorrhage. Two years later the acting manager, Michael O'Brien, was charged with cattle stealing; his defence was that the company had not paid him since O'Donovan's death. In 1949 the Reverend Sopher arrived with his wife and five children to run a home and school for Aboriginal children, part of the missionary effort of the era. Months later Mrs Sopher was badly burned when a spark from the oven caught her dress, and faced the long, agonising journey to hospital in Norseman.

By 1950, after six years of drought had stripped the station of stock, the manager Robert Mackie began converting the homestead into something travellers could use, installing petrol pumps and turning the buildings into a motel-hotel with a liquor licence. The pastoral story did not end, though. Madura ran cattle, horses, and even a small herd of camels in its time before settling into sheep. The Jumbuck Pastoral Company acquired it in 1987, and in 2016 it sold to CC Cooper & Co of Jamestown, South Australia, for a reported ten million dollars. Today it remains the second-largest sheep station in Australia, after Rawlinna, running Merinos across roughly 7,082 square kilometres of limestone country threaded with caves.