Building a bridge at Poughkeepsie proved as difficult as the Eagle predicted. The State of New York chartered the Poughkeepsie Bridge Company in 1872 with the support of Harvey G. Eastman, the city's mayor. Eastman recruited Andrew Carnegie, whose Keystone Bridge Company designed a four-pier span, but the Panic of 1873 wiped out the financing. A second attempt with the American Bridge Company of Chicago began in 1875. Pier construction started in 1876, only to hit disaster when a foundation failed in deep water. By 1878, the company was bankrupt and Eastman was dead. It took yet another group of investors to finally complete the bridge, which opened on January 1, 1889, as a double-track railroad crossing forming part of the Maybrook Line of the New York, New Haven and Hartford Railroad. For 35 years, it was the only fixed crossing of the Hudson between Troy and New York City.

The Poughkeepsie Bridge earned its keep. Advertised as the way to avoid the slow car floats and ferries of New York Harbor, it funneled freight and passengers across a river that had divided commerce since colonial times. In 1907, engineer Ralph Modjeski strengthened the bridge to handle heavier freight trains, adding a third line of trusses down the center. By 1917, the double tracks were converted to gauntlet track to center the weight of massive New Haven Railroad 2-10-2 steam locomotives, though trains still crept across at 12 miles per hour. Ownership passed through a parade of railroads: the Central New England Railway, the New Haven, Penn Central, and finally Conrail. Each owner invested less than the last. By 1974, Penn Central had neglected the bridge's fire-protection system so thoroughly that it had no water on the day a spark from a freight train ignited the wooden ties.

The May 8, 1974 fire warped the rails and ended all service, but the bridge's death was slow and bureaucratic. Penn Central applied for federal repair money. The state pledged funds. Then Conrail took ownership in 1976 and announced it would not repair the bridge, estimating the cost to reactivate the entire Maybrook route at $45.8 million. Seven years of neglect followed. Pieces of the eastern approach viaduct began falling onto Route 9 below, damaging cars. The city sued Conrail and forced it to spend $300,000 to strip the decking. Conrail abandoned the Maybrook Line in 1983 and tried desperately to unload the bridge, even suggesting a private buyer take title through a shell corporation with no assets and no insurance. The bridge passed through a succession of owners who collected rent from power lines strung along its south side, until tax delinquency finally opened the door to something new.

In 1998, a nonprofit called Walkway Over the Hudson took title to the derelict bridge, imagining a pedestrian and cyclist path above the river. The volunteer head of the organization declared it "the equivalent of the Eiffel Tower, or the Golden Gate Bridge." Skeptics scoffed, but the money materialized: the Dyson Foundation contributed nearly $20 million, New York State added $22.5 million, the federal government provided $3.5 million, and Scenic Hudson gave $1 million. Total budget reached $38.8 million. Structural engineers inspected the piers and gave them a clean bill of health. On September 5, 2009, concrete walkway slabs were laid over restored steel. On October 3, 2009, timed to the quadricentennial of Henry Hudson's voyage up the river, the Walkway Over the Hudson State Historic Park opened with music by Pete Seeger and speeches by Governor David Paterson and Senator Chuck Schumer.

The response stunned everyone. Planners had expected 267,000 visitors per year. The walkway drew 415,000 in its first three months alone. By 2017, annual visitors reached 593,868. The bridge now connects the Hudson Valley Rail Trail on the Highland side to the Dutchess Rail Trail in Poughkeepsie, forming a segment of the 750-mile Empire State Trail. A 21-story glass elevator, completed in 2014, links the walkway to the Poughkeepsie waterfront. Welcome centers opened on both ends in 2018 and 2019. The annual Treetops to Rooftops 5K race crosses the span, and on clear nights, the Mid-Hudson Astronomical Association sets up telescopes for stargazing above the river. Listed on the National Register of Historic Places in 1979 and designated a National Historic Civil Engineering Landmark in 2009, the bridge that was once ridiculed as impossible, then abandoned as worthless, has become exactly what its champions promised: a landmark on the scale of the structures it was compared to.