When the Great Western Railway wished to cross the Thames at Maidenhead,  Brunel was inclined to have two arches to take advantage of an island. The Thames Commissioners however foresaw a problem. Two arches would mean that tow ropes would have to be let go above the bridge and re-attached below. They pleaded with the railway, and Isambard Kingdom Brunel kindly said he would do, what no one else had ever dared to do, he would design the flatest widest arches ever seen. This was with a rise of only 24 ft. 6 ins from the springing to the crown and was dictated by Brunel's insistence that the railway should be virtually level.

His critics believed that this was unsafe and that it would collapse. In fact there was slight settlement when the centerings were removed but Brunel was able to persuade the contractor that this was because they had been removed before the cement was properly dry. In October 1838 the centerings were moved again but only slightly. The railway opened across the bridge in July 1839 and it was decided to leave the centerings in place for the winter. That autumn they were blown down in bad weather, revealing that they had not been supporting the bridge for some months and that trains had successfully passed over. Brunel was justified.

The first stage of the railway opened from Paddington to a temporary terminus at Maidenhead Riverside, near the Bath Road at Taplow, as the bridge was not complete. Many of the engines were delivered from Newcastle to Maidenhead by water, and then taken to Taplow. The terminus was built of wood, with platforms up on the embankment and offices down near the road, and access also possible from the road bridge. The first train ran on 31st May 1838.

The original double broad gauge tracks were converted to mixed gauge in 1861. The broad gauge ceased in 1892 and between 1890 and 1893 the bridge was widened to accommodate four standard gauge tracks. The widening was on each side but in a style exactly reproducing the original.