This seat and its neighbour Knowsley North and Sefton East are to be abolished at the next general election, following the decisions of the Boundary Commission for England. Most of Knowsley South with form the larger part of a new Knowsley constituency, except for the area around Halewood, which will become part of the new Garston and Halewood seat, and parts of Prescot and Whiston which will become part of St Helens South and Whiston.
The constituency was formed in 1983, replacing the former Huyton seat which had been held by the former Labour Prime Minister Harold Wilson since the 1950 general election. Sean Hughes of the Labour Party took the seat at the 1983 election until his death in June 1990. The ensuing by-election, held in September of that year, was won by Edward O'Hara, also of the Labour Party. O'Hara has held the seat since then.