It’s been five years since the nations last met, with Ireland running out as 38-3 winners in 2017, but they will also meet again in next year’s World Cup pool stage.
Ireland are still fresh from a historic series victory over the All Blacks in New Zealand last summer and will be among the favourites in France next year.
But defending champions South Africa will offer an immediate test in Pool B, with today’s meeting setting the tone for that battle next year.
Here’s everything you need to know.
When is Ireland vs South Africa?
The match will kick off at 5:30pm GMT on Saturday 5 November.
How can I watch it?
Like all fixtures in the Autumn Nations Series, the match will be shown live on Amazon Prime Video, which can be accessed across a range of digital devices. If you’re not an Amazon Prime Video subscriber, start a free 30-day trial here.
What is the team news?
Ireland scrum-half Conor Murray will win his 100th Test cap in Saturday’s sold-out clash with world champions South Africa after being handed his first international start for almost a year.
The 33-year-old Munster player, who fell behind Jamison Gibson-Park in the pecking order last autumn, will become his country’s eighth centurion.
Gibson-Park only makes the bench having not played since Ireland’s summer series win in New Zealand due to a hamstring issue.
Ulster wing Robert Baloucoune has been handed a third Test cap in place of the injured James Lowe, while centre Garry Ringrose will fill the void left by Bundee Aki’s suspension in the other change made by Andy Farrell.
Flanker Josh van der Flier - Ireland’s men’s player of the year for 2022 - and full-back Hugo Keenan have each been passed fit to start following injury concerns.
Meanwhile, Cheslin Kolbe will play his first test at fullback when he makes a return to the South Africa team. Kolbe, better known for runs down the wing, suffered a broken jaw against Wales in July and returns in a surprise switch by the Springboks.
Kolbe replaces Willie le Roux from the side that beat Argentina 38-21 in the Rugby Championship in September. Damian Willemse will be the flyhalf after missing the last test, replacing veteran Frans Steyn, while Kurt-Lee Arendse is on the wing for the injured Canan Moodie.
Ireland: 15. Hugo Keenan, 14. Robert Baloucoune, 13. Garry Ringrose, 12. Robbie Henshaw, 11. Mack Hansen, 10. Johnny Sexton, 9. Conor Murray; 1. Andrew Porter, 2. Dan Sheehan, 3. Tadhg Furlong, 4. Tadhg Beirne, 5. James Ryan, 6. Peter O’Mahony, 7. Josh van der Flier, 8. Caelan Doris
Replacements: 16. Rob Herring, 17. Cian Healy, 18. Finlay Bealham, 19. Kieran Treadwell, 20. Jack Conan, 21. Jamison Gibson Park, 22. Joey Carbery, 23. Stuart McCloskey
South Africa: 15. Cheslin Kolbe, 14. Kurt-Lee Arendse, 13. Jesse Kriel, 12. Damian de Allende, 11. Makazole Mapimpi, 10. Damian Willemse, 9. Jaden Hendrikse; 1. Steven Kitshoff, 2. Malcolm Marx, 3. Frans Malherbe, 4. Eben Etzebeth, 5. Lood de Jager, 6. Siya Kolisi (captain), 7. Pieter-Steph du Toit, 8. Jasper Wiese
Replacements: 16. Bongi Mbonambi, 17. Ox Nche, 18. Vincent Koch, 19. Franco Mostert, 20. Deon Fourie, 21. Kwagga Smith, 22. Faf de Klerk, 23. Willie le Roux