The UK's Daily Mail has a decent explanation and creepy photos of how the southernmost city in Illinois went from a thriving (and historical) port to a nearly-abandoned shell in 50 years:
The town's luck began to fall in 1889 when the Illinois Central Railroad bridge opened over the Ohio River - although much railroad activity was still routed through the town, so its effects were not severe.
The same can't be said for a second bridge that opened around 23 miles up the Mississippi at Thebes, Illinois in 1905.
The completion of that bridge drained away much railroad activity, reducing the need for the ferries that once carried railroad stock.
And with steamboats being phased out in favor of barges, Cairo was no longer the essential hub it had once been. The end had begun.
The town was hit again in 1929 and 1937 when bridges were completed across the Mississippi and Ohio rivers, respectively, allowing a route through for US Routes 51, 60 and 62.
As the bridges were built at the town's southern tip, it was easy for traffic to bypass Cairo completely, draining away more money.
But there was still a little money coming to the town until 1987, when the Interstate 57 bridge opened across the Mississippi, allowing traffic to bypass the town altogether - killing its hotel and restaurant industries.
I visited Cairo in 2003. It was pretty dead then, but judging by the photos in the Daily Mail article, it's even worse now.
Here's the confluence of the rivers, in December 2003: