Thirteen rail cars were strewn across the tracks at the derailment site, District of Columbia Fire Department photos show.
A ruptured tank car likely leaked several thousand liters of sodium hydroxide, a caustic substance used to produce household products including paper and detergent, before the leak was plugged, deputy fire chief John Donnelly told a news conference.
The fire department did not order evacuations around the site of the accident, which happened about 5km from the White House near the Rhode Island Avenue station.
Washington Mayor Muriel Bowser said it would take some time for CSX and emergency workers to clear the overturned cars and clean up the spill.
"There's nothing running on that track tomorrow," Bowser said.
She added that no cause for the accident had been determined, but a federal investigation into the derailment had begun.
The derailed train was travelling from Cumberland, Maryland, to Hamlet, North Carolina. It was made up of three locomotives and 175 rail cars.
A spokesman for the region's Metro transit system said service would be restored as soon as the hazardous materials were cleared from the area and safety tests conducted on the Metro rails.
The chemical spill could stir controversy over CSX transporting hazardous materials through the heart of the US capital.
Over the past five years, some residents and community groups opposed a major CSX construction project to rebuild and expand a 112-year-old rail tunnel in central Washington, fearing it would encourage more freight traffic through the city and increase chances of a chemical spill.
Construction on the US$170 million project has begun after several unsuccessful court challenges.