Brunel's father, Marc Brunel (1769–1849), a French emigré and distinguished engineer, arrived in England in 1799. He sent his son to Paris in 1820 to learn mathematics and engineering. Brunel returned to England in 1822 to work for his father and in 1825 they began the construction of the Rotherhithe-Wapping tunnel underneath the Thames. Here Brunel quickly learned of the unpredictability of great engineering projects; the tunnel flooded in 1828 and Brunel nearly drowned.

While convalescing, he heard that the city of Bristol was considering building a bridge across the River Avon. A competition was to be held with Thomas Telford as the judge. Brunel submitted plans for a suspension bridge at Clifton. Telford rejected Brunel's design and proposed instead that he himself should build something more appropriate. The selection committee, however, preferred Brunel's plans. Although work began in 1831 it was not until 1864, well after Brunel's death, that the bridge was opened. The span is still standing and remains, perhaps, Brunel's most durable monument.

While in the Bristol region other commissions came his way. In 1833 he was invited to build the Great Western Railway (GWR) to run between London and Bristol. He decided to adopt a 7-foot gauge rather than the 4 foot 8½-inch gauge introduced by George Stephenson at the beginning of the railway age. The broad gauge enabled trains to run faster and more comfortably. It did not, however, allow the GWR to link up easily with the rest of the growing network. The line was opened in 1841 and extended to Exeter by 1844. It was insisted, however, in the interest of establishing a unitary railway system, that after 1846 no more broad-gauge track could be laid down. The last of the track was removed in 1896.

Not all Brunel's projects were as successful – in particular, the ‘atmospheric railway’ that he built between Exeter and Newton Abbot in the 1840s. The idea was to eliminate the locomotive. A continuous pipe was laid between the rails and attached to the carriages by a suspended piston. Air was evacuated from the pipe by pumping engines located along the route. In practice, it proved too difficult to maintain the leather seal through which the connecting rod emerged; it was either eaten by rats, or made brittle by the sea air, or it froze in winter. The line was opened in November 1847 and closed the following year, having incurred enormous losses.

Brunel also turned his attention to steamships. The first Atlantic steam crossing had been accomplished by the American Savannah in 1819 using steam in combination with sail. Conventional wisdom held that to cross the Atlantic on steam alone would require so much coal as to leave no room for freight. Brunel calculated otherwise and dispelled this myth with his Great Western (1837; 2340 tons), a timber ship driven by paddles. It crossed the Atlantic in 15 days with 200 tons of coal unused in its bunkers.

Brunel went on to build the equally revolutionary Great Britain (1843; 3676 tons) with an iron hull and screw propellor, which continued in service for 30 years. His final work was the Great Eastern (1858; 32,000 tons) with its double iron hull, screws, and paddles; it was later used to lay the first transatlantic telegraph cable.

The struggle to complete the Great Eastern against considerable financial and engineering difficulties seems to have ruined Brunel's health and probably caused the stroke he suffered soon after his great ship had been finally launched. He died soon after.