The bones, believed by some to have medicinal benefits, were destined for Malaysia.
Officials have seized 342kg (754lb) of lion bones and arrested three people at Johannesburg airport in South Africa, the environment ministry said.
The bones, which are prized in Asia for supposed medicinal benefits and to make jewellery, were destined for Malaysia.
The 12 boxes of lion bones wrapped in aluminium foil were misdeclared and discovered upon inspection.
Exporting bones of lions bred in captivity is legal in South Africa, though a special permit is required.
Ministry spokesman Albi Modise said those arrested were foreigners, including two from Zimbabwe, with one suspect still in custody.
The average weight of a lion skeleton is 9kg, according to a report produced by South Africa’s EMS conservation foundation and the Ban Animal Trading group.
With skeletons of average weight, 342kg would amount to 38 lions.
It was not immediately clear whether the bones were from lions bred in captivity or from the wild.
Lion parts are often sold in Asian markets mislabelled as tiger parts, due to China’s ban on the sale of tiger products, according to the UK-based Environment Investigation Agency.
“Tiger bone wine” is used in traditional Chinese medicine, though there is no evidence it has any benefits.
More than 11,000 lions live in South Africa, with 3,000 of them located in national parks where hunting is forbidden.