Secretary of State for Scotland, Willie Ross MP cuts the ribbon at the opening of Stage 1 on 2nd December 1966. The project saw immediate reductions in journey times and accident rates, removing thousands of vehicles from the substandard A74.

Until recently there had been very few alterations to the original Hamilton Bypass route. Connections to the M73 opened in mid-1971 with SOS phones and central reserve barriers added throughout the rest of that decade. In the early 1980s the Hamilton and Bothwell Service areas opened. These has been intended open shortly after the route was completed. In the late 80s the A74 south from Draffan was converted to motorway standards and the section between Maryville and Hamilton was illuminated. Completion of the Bellshill Bypass and the East Kilbride Express dramatically increased the importance (and traffic flows) through Raith Interchange. The late 80s also saw the junctions of the route renumbered. Initially they were numbered from south to north, reversed when the motorway began to expand towards Carlisle.

The first significant changes occurred in the early 1990s when alterations were made at Maryville to accommodate the motorway as it was extended northwards into Glasgow. At the same time concrete overhead sign gantries were added, extending the Glasgow CITRAC control system into Lanarkshire. Major refurbishment work of Raith Bridge over the River Clyde was undertaken in the early 2000s.

By the mid-2000s parts of the route were starting to experience congestion. This was focussed on the northbound carriageway approaches to both Raith Interchange and Maryville. Southbound queues were common on the approach to Hamilton. Traffic flows had increased to more than 90,000 vehicles per day, mostly as a result of increases in peak time commuter traffic. As part of traffic modelling for the M74 Completion and M8 Baillieston to Newhouse schemes, it was identified that additional congestion would be likely at Maryville and on the M74 as traffic behaviour changed. Additionally, congestion at Raith Interchange had steadily worsened since the completion of the East Kilbride Expressway, with the junction increasingly over capacity. Plans for an underpass for A725 traffic had been considered since the early 1990s.

By the early 1990s, traffic congestion at Raith Interchange, or Junction 5, led to improvement studies. In 2014, construction commenced on an underpass to cater for through traffic. This, in conjunction with other improvements, resulted in a considerable improvement in journey times.