After graduating from the polytechnic school in Berlin, Roebling worked for the Prussian government for three years and at the age of 25 emigrated to the U.S. He settled with others from his hometown in a small colony that was later called Saxonburg, near Pittsburgh, in the hills of western Pennsylvania. He married the daughter of another Mühlhausen emigrant, and they had nine children. After a few years of unsuccessful farming, John Roebling went to the state capital in Harrisburg and applied for employment as a civil engineer.

He had often watched canalboats being hauled over hills from one watershed to another, and he persuaded the canal commissioners to let him replace the hempen hawsers with wire cables. He developed his own method for stranding and weaving wire cables, which proved to be as strong and durable as he had predicted. The demand for such cable soon became so great that he established a factory to manufacture it in Trenton, N.J. This was the beginning of an industrial complex that finally was capable of producing everything from chicken wire to enormous 36-inch (91-centimetre) cables. It remained a family-owned business, carried on by three generations of Roeblings.

Work on the bridge cost Roebling his life. He was taking final compass readings while standing on some pilings at a ferry slip and did not notice that a boat was docking. As it banged into the slip, one of his feet was caught between the pilings. He was rushed to his son's house in Brooklyn Heights, where the doctors amputated his injured toes. Three weeks later, he died of tetanus at the age of 63. His son carried on his work on the Brooklyn Bridge.