The GWML was built by the original Great Western Railway company between 1838 and 1841, as a dual track line in the 7 ft (2,134 mm) broad gauge.

During the mid-1990s, a stretch of the GWML between London Paddington and Hayes & Harlington was electrified using 25 kV AC overhead lines for the Heathrow Express.

Due to budget overruns, the British government deferred electrification of the section through Bath Spa from Royal Wootton Bassett to Bristol in 2016.

Communities served by the GWML include West London (including Acton, Ealing, Hanwell, Southall, Hayes, Harlington and West Drayton); Iver; Langley; Slough; Burnham; Taplow; Maidenhead; Twyford; Reading; Tilehurst; Pangbourne; Goring-on-Thames; Streatley; Cholsey; Didcot; Swindon; Chippenham; Bath; Keynsham; and Bristol.

The construction of what would become the GWML was motivated by several factors, one of the more influential being the sizeable merchant community of Bristol, which keenly advocated for such a railway to be built to help maintain the city's position as the second port of the country as well as the chief one for American trade.

[6] Part of the route passes through and contributes to the Georgian Architecture of the City of Bath World Heritage Site; the path through Sydney Gardens has been described as a "piece of deliberate railway theatre by Brunel without parallel".

Dual gauge was introduced as follows: London to Reading (October 1861), Reading to Didcot (December 1856), Didcot to Swindon (February 1872), Swindon to Thingley Junction, Chippenham (June 1874), Thingley Junction to Bathampton (March 1875), Bathampton to Bristol (June 1874), Bristol station area (May 1854).

[5][12] Between 1877 and 1899, the original dual tracks were widened to four in numerous places, mainly in the east half of the line: Paddington to Southall (October 1877), Southall to West Drayton (November 1878), West Drayton to Slough (June 1879), Slough to east side of Maidenhead Bridge (September 1884), Maidenhead Bridge to Reading (June 1893), Reading station (1899), Reading to Pangbourne (July 1893), Pangbourne to Cholsey and Moulsford (June 1894), Cholsey and Moulsford to Didcot (December 1892); also short sections between Didcot and Swindon, and at Bristol.

These included the Warship locomotives, which were based on proven West German designs, the British-designed Class 14, Hymek and Western types.

In the mid-1990s, the line between London Paddington and Hayes & Harlington was electrified as part of the Heathrow Express scheme, which was officially launched in June 1998.

[34] Communities served by the Great Western Main Line include West London (including Acton, Ealing, Hanwell, Southall, Hayes, Harlington and West Drayton); Iver; Langley; Slough; Burnham; Taplow; Maidenhead; Twyford; Reading; Tilehurst; Pangbourne; Goring-on-Thames; Streatley; Cholsey; Didcot; Swindon; Chippenham; Bath; Keynsham; and Bristol.

A junction west of Swindon allows trains to reach Bristol by an alternative route along the South Wales Main Line.

The stations served by trains between London Paddington and Bristol Temple Meads are Reading, Didcot Parkway, Swindon, Chippenham, and Bath Spa.

Great Western Railway also operate a train between London Paddington – Cardiff Central every 30 minutes, with hourly extensions to Swansea.

At Swansea/Cardiff there is a connecting Transport for Wales boat train to/from Fishguard Harbour for the Stena Line ferry to Rosslare Europort in Ireland.

Between Didcot and Royal Wootton Bassett, a series of passing loops allow fast trains to overtake slower ones.

This section is signalled for bi-directional running on each line but this facility is usually only used during engineering working or when there is significant disruption to traffic in one direction.

[45] Reading railway station saw a major redevelopment with new platforms, a new entrance, footbridge and lifts; the work was completed a year ahead of schedule[46] in July 2014.

[49][50][51] Following delays to the work and a large increase in costs,[52] the Conservative government announced in July 2017 that, for the time being, electrification would only be completed as far as Thingley Junction, 2 miles (3.2 km) west of Chippenham.

[57] Other more distant aspirations include resignalling and capacity improvements at Reading; the provision of four continuous tracks between Didcot and Swindon (including a grade-separated junction at Milton, where the westbound relief line switches from the north side of the line to the south); and resignalling between Bath and Bristol to enable trains to run closer together.

[61] Signalling Solutions is to resignal the 12 miles (19 km) from Paddington to West Drayton, including the Airport branch, as part of the Crossrail project.

[65] Oxfordshire County Council included a proposal for a new station to serve Wantage and Grove in their 2015–2031 local transport plan.