The road received a substantial upgrade in the early 19th century under the direction of Thomas Telford, who made significant engineering improvements, including a new route over the Beattock Summit and the Metal Bridge just in England just south of the border.

[1] The last remaining section of all-purpose road on Telford's original alignment, the so-called "Cumberland Gap" between Carlisle and Metal Bridge, was replaced by a motorway in 2008 after years of delays due to a breakdown in discussions between the Westminster and Scottish governments.

Currently the A74 is a suburban route of local importance that links the Gorbals and Broomhouse districts of Glasgow, via neighbourhoods in the city's East End.

Several high-profile accidents occurred, most notoriously the debris of Pan Am Flight 103 in December 1988, which partially fell on the road near Lockerbie and caused several fatalities.

It left this sparsely populated section in the Southern Uplands and entered the Clydesdale communities of Lesmahagow, Kirkmuirhill and Larkhall, crossing the River Avon into Hamilton.

[6] According to contemporary Ordnance Survey mapping, the A74 starts in the Gorbals as Ballater Street, meeting the A8 (the A728 also starts here) and crosses the Clyde at the King's Bridge, runs through Glasgow Green and into the East End suburbs (Bridgeton, Celtic Park football stadium / Parkhead, Lilybank, Braidfauld, Foxley and Mount Vernon, all as London Road), then becoming Hamilton Road and running eastwards as far as Broomhouse where it ends at the Black Bear Roundabout, a feeder for the M74 Junction 3A (Daldowie).

The road continues as the dual carriageway A721 for a short distance underneath the elevated lanes of the M73 Maryville Interchange until a small roundabout towards either Birkenshaw (B7001) or Uddingston – the latter route becomes the A74 again (on its original alignment) for a matter of a few hundred yards to Powburn junction, where New Edinburgh Road eastwards then takes on the A721 designation leading on to Viewpark and Bellshill, while Uddingston Main Street southwards downgrades to the B7071.

[6] Due to its continued status as one of the most important connections between England and Scotland, talks began in the 1950s to improve its quality to cater for modern motor traffic.

While a 4+1⁄2-mile (7.2 km) section of dual carriageway had already been completed before World War II, Tom Steele, then MP for Lanark, was particularly keen on the entire route from Carlisle to Uddingston being dualled before the mid-1960s.

[32] After years of political battles between the English Highways Agency and the Scottish Executive, followed by a lengthy design and public enquiry phase,[30] the "M6 Motorway Extension Carlisle to Guards Mill" became part of the government's targeted plan of improvements in 2002, with the intention to start work around 2005–06 at a cost of £65 million.

[33] Due to delays with the G8 Conference in 2005,[34] construction work started on 25 July 2006, and included a replacement for the 1971 Metal Bridge, and a new VOSA testing site.

[43] On 22 December 2004, a major road accident occurred on the Cumberland Gap section of the A74 near Metal Bridge, after high winds tipped a lorry travelling southbound onto the opposite carriageway, causing it to collide with two other goods vehicles.

David Maclean, MP for Penrith and The Border, said "I'm fed up nagging about the Cumberland gap", adding "I know the government considers railways to be a higher priority, but Cumbria cannot survive without decent roads.

"[44] In August 2008, when the A74 was still an all-purpose road across the Cumberland Gap, the Highways Agency took out a special order to ban cyclists and pedestrians from the route, advising them to use the A7 to Longtown instead.

[45] In December 1988, the A74 around Lockerbie received international media attention, when Pan Am Flight 103 was destroyed by an explosive device above the town, scattering debris around the local area.

The wing section of the aircraft landed in Sherwood Crescent, which runs parallel to what was then the A74 Lockerbie Bypass, destroying houses and striking several vehicles.

[46] According to eyewitness reports, the resulting fires caused cars to be set alight on the road, and took "a huge bite out of the southbound lane".