Former Army officer Henry Worsley will endure freezing temperatures during the 80-day trek over 1,100 miles (1,770km).
The 55-year-old will pull a sledge containing his food, tent and equipment and he will not receive supply drops or help across the ice from dogs.
He sets off in November and wants to raise Â£100,000 for the Endeavour Fund.
The organisation helps injured and sick servicemen and women.
Mr Worsley told BBC Radio 4's Today programme that he expected to lose two stone (12.7kg) during the challenge.
"There is no black art to driving one ski in front of the other," he said.
"What is driving me on is the money for these wounded soldiers."
Mr Worsley flies to Chile on Tuesday and from the country's southernmost tip will fly to Union Glacier in early November, his Antarctic logistics base.
He will then continue to his start point at Gould Bay - the closest accessible point to Shackleton's intended start at Vahsel Bay on the edge of the Weddell Sea.
Shackleton and his team's hopes of becoming the first explorers to cross the Antarctic continent were crushed after his ship, Endurance, was trapped by pack ice, leaving the men stranded in 1915.
The Duke of Cambridge, who is patron of the challenge, presented Mr Worsley with a replica of the same flag Shackleton was given before his expedition, which will be taken on the trek.
He told Mr Worsley: "It's a huge challenge, but there's no better person than you, we'll be thinking of you at Christmas."
An explorer is hoping to complete Sir Ernest Shackleton's unfinished journey to the South Pole to become the first person to cross the Antarctic unaided.