The discoveries near Hamilton in South Lanarkshire include coins believed to date from the 10th or 11th century, and fragments of glazed medieval pottery and clay smoking pipes.
They were found under the motorway verge near junction six, opposite the Hamilton Services.
It came during work to widen that stretch of the M74 as part of the £500 million improvements to the motorway and nearby M73 and M8 by Transport Scotland.
The Scottish Government agency said archaeologists believed this could finally identify the location of the lost village of Cadzow – now part of Hamilton.
James II gave permission for Cadzow to be renamed Hamilton in 1445, after the Dukes of Hamilton, who owned lands in the area.
Archeologists said the site may have lain undisturbed because it was where the Netherton Cross, which also dates from 10th or 11th century, once stood,