The acclaimed author, from Leeds and who worked at the Yorkshire Evening Post, will return to the family saga in Blackie And Emma, due out in 2020.
Bradford was spurred on to revisit the story by the death of her "beloved" husband Bob this year.
Opening five years before A Woman Of Substance, it will tell the tale of a 13-year-old Blackie O'Neill who faces an uncertain future in rural Co Kerry, Ireland.
Orphaned and alone, he has just buried his sister Bronagh and must leave home to set sail for England in search of a better life with his mother's brother in Leeds.
Before long he meets a kitchen maid called Emma Harte on the Yorkshire moors.
Hollywood star Liam Neeson played O'Neill in a 1985 three-part TV miniseries adaptation.
The announcement comes on the 40th anniversary of the original book's publication.
Bradford said: "After my beloved husband, Bob Bradford, died in the summer, Blackie O'Neill came back into my head.
"Bob was by my side at the beginning when I wrote A Woman Of Substance and I felt compelled to tell Blackie's story.
"The true Blackie O'Neill will be revealed and fans of Emma Harte will be able to live his tumultuous life with him."
Publishers HarperCollins promised that the book will reveal the true O'Neill, "his tumultuous life, the obstacles facing him, the desire he has to throw off the impotence of poverty and move up in the world".
A Woman Of Substance was first published in 1979, and has sold more than 30 million copies worldwide.
Publishing director of general fiction Lynne Drew said: "Blackie and Emma is the kind of idea that gives an editor goosebumps.
"When Barbara rang me to tell me she wanted to write Blackie's story I could immediately hear the excitement in her voice - and knew the fans would go wild.
"I can't wait to bring the never-before-told story of Blackie and Emma out into the world."