In 1846 the Cornwall Railway Act received Royal Assent, stipulating that the ferry at Saltash should be replaced by a railway bridge to link Cornwall to the rest of the UK by rail. Isambard Kingdom Brunel was appointed as chief designer and engineer, his challenge to build a bridge to span the River Tamar which at this point is some 335 m (1100 ft) wide.

At first he intended to construct a single span bridge of 256 m (850 ft) but the constraints imposed by the Admiralty ruled this out. These demanded the deck of the bridge be 33 m (100 ft) above high tide and that the river remain fully operational to the Navy at all times. His second plan was for a bridge with two spans of 100 m (300ft) and two spans of 670 m ( 200ft), but after investigation it was found that there was no suitable bedrock on which to build the three piers.

Finally he decided that the bridge should have a single pier mid stream which would support two spans of 139 m (455ft). The railway would then have to be supported by a further ten approach spans on the Cornwall side and seven on the Devon side. There was however nowhere to secure the tension chains, so Brunel had to design a bridge with self supporting trusses. His solution was oval shaped arched trusses that rest on top of the piers. In order to prevent the piers from being pushed outwards, chains were hung and eleven girders were used to connect the trusses to the chains. The deck was then suspended from the braced chains at twenty two points.

It was originally intended to carry a two way track but the Cornwall Railway Company had insufficient funds - the reduction to a single track saved £100,000. After the first contractor went bankrupt, Brunel decided to take on the contract himself. During the construction of the London Tunnel, his father Marc Brunel had used a form of diving bell with compressed air. Brunel adapted this for work on his bridge. He built a cylinder which was floated into the middle of the river and sunk. The water was pumped out and the top sealed. Compressed air was then pumped into the cylinder to allow up to 40 men to work within the tube. First they had to excavate 3.6 m (12 ft) of mud followed by 1 m (3 ft) of rock before a suitable foundation was located. Work then began to build the central tower of brick.

On July 4th 1853 the foundation for the first of the Cornish piers was laid by the Mayor of Saltash Mr W Rundle in Silver Street. The central pier was capped in 1856 and work then began to erect the four octagonal columns which were to hold the deck. On September 1st 1857, watched by some 20,000 spectators, the first truss was floated out into the centre of the river supported by two barges. It took two hours, five navy vessels and 500 men to manoeuvre them through 45 degrees, where as the tide turned they then sank into position on to the piers.

The truss was gradually raised at a rate of  2 m (6 ft) a week using hydraulic jacks until on 1st July 1858 it reached its final height 33 m (100 ft) above the water. On July 10th 1858, the second span for the Devon side was floated out into the river. Word had spread about this amazing feat of engineering and special trains were laid on to bring spectators from London. Brunel by this time was too ill to attend.

The first test train, a South Devon Locomotive, crossed the bridge on 11th April 1859. His Royal Highness Prince Albert officially opened the bridge on 2nd May 1859. After visiting Coombe viaduct (at that time constructed of wood) he returned to Saltash station and walked back across the bridge to Devon to declare the bridge officially open. Brunel finally crossed his bridge on an open wagon two days later. He died on 5th September 1859.

In 1905, 401 new cross-girders were fitted to permit the passage of heavier locomotives. In 1908, the two spans nearest Saltash railway station were replaced with wider ones to accommodate a new track layout. The remaining approach spans were replaced on both sides of the river during 1928 and 1929. During the 1930s new cross-bracing and diagonal sway-bracing were added between the vertical standards to further strengthen the bridge and keep the suspension chains hanging in the correct shape. In 2011, a programme to strengthen and refurbish the bridge commenced, involving the replacement of 50,000 bolts and the application of twelve layers of paint to prevent further corrosion.  

The structure is Listed Grade 1.