Monsignor Leo Cushley, from Lanarkshire, will be ordained as the Archibishop of St Andrews and Edinburgh tomorrow at St Mary's Cathedral in the capital.
Principal consecrators will be Cardinal James Michael Harvey of the Basilica of Saint Paul Outside the Walls, UK Papal Nuncio Antonio Mennini and Archbishop Philip Tartaglia of Glasgow.
His ordination follows one of the most turbulent periods for the Catholic Church in modern history.
Cardinal O'Brien stepped down in February after three priests and a former priest made allegations of inappropriate behaviour against him.
He issued an apology, saying, "there have been times that my sexual conduct has fallen below the standards expected of me."
Mgr Cushley, who was born in Airdrie, will begin individual conversations with the 100-plus priests in the Archdiocese next week.
With Cardinal O'Brien maintaining pockets of support across the Archdiocese, and his replacement stating at the weekend that the former Archbishop should not return to Scotland, Mgr Cushley will need to build bridges.
Other issues facing the former Vatican diplomat include opening the books on allegations of historic sex abuse and a possible shake-up of the Bishop's Conference.
A church spokesman said: "We are looking forward with some excitement and anticipation to the installation of Monsignor Cushley as Archbishop.
"It comes against a backdrop of nearly 20 years in the diplomatic service. He now finds himself back on home turf, somewhere where he least expected to be."