The Merchistonians and the Academicals will meet at Raeburn Place, the venue of the first international rugby match between Scotland and England in 1871.
The senior sides, which were founder members of the Scottish Rugby Union, last played in 1884 but since then the rivalry has been restricted to school sides from Merchiston Castle and Edinburgh Academy.
And the significance of the occasion has not been lost on both sides, who will be playing to raise funds for Hearts & Balls, a charity which provides for players who have suffered grievous injury on the sportsfield and their families.
Famous figures will also be mucking in to mark the historic occasion, with former Scotland coach Frank Hadden coaching the Merchistonians, and former Scotland flanker David McIvor coaching the Academicals.
Mr Hadden said: “I’m honoured to be involved in the rebirth of the fixture and to be a part of what should be a great day for a very worthwhile cause.
“I’m excited to see this historic rivalry play out at Raeburn Place,” Mr McIvor added.
Former Scotland internationals Duncan Hodge, Craig Joiner and Stuart Moffat will also be offering their support on the day in a bid to raise extra cash for the charity which was founded in 1999 after a Lismore Rugby Club player was paralysed by a spinal injury during a game.
Since then, the charity has supported more than 30 players and their families, including help with legal costs, adapting a home and providing mortgage interest payments for a bereaved widow and her young family.
Jim Littlefair, director of the charity, said: “We would like to congratulate those who have reformed one of the most historic rugby ties in Scotland.”
The match will be free to spectators with a 2pm kick-off. A bar and barbeque will also be open from midday until 5pm.
For more information visit www.heartsandballs.org.uk.