Iberia will fly from London to Johannesburg, via Madrid, from August 2016.
The British Airways sister airline will fly three times a week, on Mondays, Thursdays and Fridays.
The return flight will operate on Tuesdays, Fridays and Saturdays.
Schedules are designed with London connections in mind.
Iberia will use the A330-300 on the route, which can accommodate up to 36 passengers in business class and 242 in the economy.
To mark the launch, Iberia is offering a special fare starting at £956 for a return flight from London including taxes, fees and carrier charges.
