The line only became a through route on 2 July 1906 when the Langport and Castle Cary Railway was completed.
Before this, from 5 May 1848, through trains from London to Plymouth had run via Bristol Temple Meads: this is often called the "Great Way Round" and a few trains still take this route.

The various sections of line were opened: 
Exeter to Teignmouth – 30 May 1846
Teignmouth to Newton – 30 December 1846
Newton to Totnes – 20 July 1847
Totnes to Laira – 5 May 1848
Laira to Plymouth – 2 April 1849
The Reading to Hungerford section was promoted as the Berks and Hants Railway; from there to Patney & Chirton by the Berks and Hants Extension Railway; and from Westbury to Castle Cary by the Wilts, Somerset and Weymouth Railway.
The section from Cogload Junction to Exeter was built by the Bristol and Exeter Railway, which company's Yeovil branch became part of the new main line between Curry Rivel Junction and Athelney Junction, and including Athelney station.
The section between Exeter and Plymouth was built by the South Devon Railway Company.

The nominally independent companies had all been amalgamated into the Great Western Railway by 1 February 1876, and the remaining 7 ft ¹⁄₄ in (2,140 mm) broad gauge lines were closed on 20 May 1892 and converted to 4 ft 8 ¹⁄₂ in (1,435 mm) standard gauge over the following weekend.
 A series of cut-off lines were constructed during the following 15 years which saw the through route established.
 The Great Western was nationalised on 1 January 1948 as part of the new British Railways.

In 1977 the Parliamentary Select Committee on Nationalised Industries recommended considering electrification of more of Britain's rail network, and by 1979 BR presented a range of options to do so by 2000.
Some included electrifying the Bristol to Exeter line, Exeter to Plymouth Line, Riviera Line and Cornish Main Line.
Under the 1979–90 Conservative governments that succeeded the 1976–79 Labour government the proposal was not implemented.
Currently, there are no proposals to electrify the line.

Resignalling in the 1980s allowed faster running.
This was followed by privatisation in the 1990s, being transferred first to Railtrack and then to its successor Network Rail.
The line only became a through route on 2 July 1906 when the Langport and Castle Cary Railway was completed. Before this, from 5 May 1848, through trains from London to Plymouth had run via Bristol Temple Meads: this is often called the "Great Way Round" and a few trains still take this route.
The various sections of line were opened: 
Exeter to Teignmouth – 30 May 1846
Teignmouth to Newton – 30 December 1846
Newton to Totnes – 20 July 1847
Totnes to Laira – 5 May 1848
Laira to Plymouth – 2 April 1849
The Reading to Hungerford section was promoted as the Berks and Hants Railway; from there to Patney & Chirton by the Berks and Hants Extension Railway; and from Westbury to Castle Cary by the Wilts, Somerset and Weymouth Railway. The section from Cogload Junction to Exeter was built by the Bristol and Exeter Railway, which company's Yeovil branch became part of the new main line between Curry Rivel Junction and Athelney Junction, and including Athelney station. The section between Exeter and Plymouth was built by the South Devon Railway Company.
The nominally independent companies had all been amalgamated into the Great Western Railway by 1 February 1876, and the remaining 7 ft ¹⁄₄ in (2,140 mm) broad gauge lines were closed on 20 May 1892 and converted to 4 ft 8 ¹⁄₂ in (1,435 mm) standard gauge over the following weekend.  A series of cut-off lines were constructed during the following 15 years which saw the through route established.  The Great Western was nationalised on 1 January 1948 as part of the new British Railways.
In 1977 the Parliamentary Select Committee on Nationalised Industries recommended considering electrification of more of Britain's rail network, and by 1979 BR presented a range of options to do so by 2000. Some included electrifying the Bristol to Exeter line, Exeter to Plymouth Line, Riviera Line and Cornish Main Line. Under the 1979–90 Conservative governments that succeeded the 1976–79 Labour government the proposal was not implemented. Currently, there are no proposals to electrify the line.
Resignalling in the 1980s allowed faster running. This was followed by privatisation in the 1990s, being transferred first to Railtrack and then to its successor Network Rail.
Exeter–Plymouth line