Reg next worked for the South Australian Geological Survey, who sent him to reopen the Radium Hill Uranium Field in 1944, and to map the Mount Painter uranium field. At the time, uranium was believed to be rare, and was required for the Manhattan Project. Uranium from these mines were used to manufacture British nuclear weapons but was not ready in time for the first atomic bomb.
When Reg discovered the fossils at Ediacara Hills in 1946 the sun was low in the sky, thus able to cast shadows increasing the visibility of the shallow fossil impressions on the rocks. He realised that these fossils were very ancient, either of Early Cambrian, or possible even of Precambrian age. He published and promoted his finds, and subsequent work by Prof Martin Glaessner at the University of Adelaide demonstrated that they were indeed of latest Precambrian age. Although Precambrian animal fossils had been reported before, they had not been universally accepted as organic. This discovery led ultimately to the recent erection of the Ediacaran Period, the first new geological period created in over one hundred years.
In 1951 he married Griselda Paterson and fathered two children, Margaret and Douglas.
Of other significance, he helped set up SANTOS (South Australia Northern Territory Oil Search), which discovered the gas deposits in Cooper Basin, including the Moomba Gas Field. This supplies natural gas to New South Wales and Canberra. He was granted the Officer of the Order of Australia in 1983. He owned the company Geophysical Surveys which was a consulting and contracting company for geological and geophysical work. They prospected for uranium in the Northern Territory and nickel in the north west corner of South Australia as well as working for SANTOS.
In 1962 Geophysical Surveys became incorporated into Beach Petroleum.
In 1968 Sprigg purchased Arkaroola, a property in South Australia, and turned it into a wildlife refuge and tourist attraction.
The Royal Society of South Australia awarded him the Verco medal in 1968.