The South Africans, along with one Zimbabwean, were intercepted by police on Saturday while carrying weapons and veterinary drugs in the southern Gwembe district.
Zambia Wildlife Authority spokesman Zacks Kalembwe told AFP that the men were towing a vehicle “laden with 12 sable antelopes”.
According to the South African Times newspaper, the group were arrested as they were off-loading the animals to put them into a light aircraft at a remote dirt airstrip.
Sable antelope are prized for their rarity and long horns, with one bull sold for nearly $2 million at auction in South Africa last month.
Kalembwe told the Times that the South Africans had been tracked since they entered Zambia on October 5.
“Our authorities flagged them and alerted the game reserves and law enforcement authorities,” he said.
“We followed them to a ranch, where 40 sable antelope were being kept.”
Kalembwe said it was “the most complex wildlife smuggling syndicate” that the police had broken up, adding that the aircraft had been specially adapted to carry animals.
The six suspects are expected to appear in court later this week.
Last month, three South Africans were arrested and charged for trying to smuggle 29 sable out of Zimbabwe into South Africa.