Carol Fox, 35, will take over on October 28, when Mr O'Neill steps down. She has been London regional officer with the public-sector union Unison since 1993, responsible for local government, the health service and the voluntary sector.
Ms Fox has worked as a social worker in Lothian, Strathclyde and the London borough of Tower Hamlets. Before moving to London, she spent four years with Women's Aid in Hamilton. Ms Fox, a native of Motherwell, attended Holy Cross High in Hamilton and is a graduate of Glasgow University.
She was selected from a shortlist of seven, which included NASUWT Scottish leaders, Tino Ferri and Jack Duffy.
Mr O'Neill, who is to become a full-time councillor in East Ayrshire, where he is secretary of the ruling Labour group, said the union previously had made officer appointments outside its own ranks. "It is in line with our view that we are a trade union, and part of the wider movement, not just an educational institute," he said.