It passes underneath the National Mall near the US Capitol and ends at a junction with US 50 at New York Avenue, roughly one mile (1.6 km) north of the 3rd Street Tunnel.

This moniker causes confusion, because the intersection of I-395, Washington Boulevard, and State Route 244 (SR 244; Columbia Pike) several miles north was historically known by that name and continues to be recognized by the Virginia Department of Transportation (VDOT) as such.

A 2007 survey found that during the morning rush hour, the HOV lanes carry about 65 percent of travelers on I-395 (61,000 commuters), including 32,000 in transit busses and 29,000 in private vehicles with two or more people.

I-395 follows a depressed roadway (the Center Leg Freeway), which was placed underground in 2019, that has three more partial interchanges (exits 8, 9, and 10) with local streets before terminating at New York Avenue/US 50.

Originally SR 350, the full length of the Henry G. Shirley Memorial Highway was opened on September 6, 1949, from south of the Pentagon to Woodbridge, Virginia,[4] along what is now better known as the I-95 corridor.

Original plans called for I-95 to travel through Washington DC and Prince George's County, Maryland, toward the northeastern portion of the Capital Beltway, from which I-95 presently continues its northbound route.

The DC government finalized a deal in 2010 with Louis Dreyfus Company to construct a 2.1-million-square-foot (200,000 m2) mixed-use development in the airspace over the Center Leg Freeway portion of I-395.

[6] In 2015, work began on I-395 in conjunction with Capitol Crossing, a major real-estate project in DC, part of which lies on top of the highway.

The work involves adding a $200-million (equivalent to $251 million in 2023[5]) concrete platform that connects neighborhoods that have been severed by the freeway, creating a better community atmosphere in the eastern edge of downtown.

[11] In December 2023, VDOT permanently closed Exit 9 for Clark St as part of construction on Boundary Channel Drive.

"[14] VDOT is also building new pedestrian and bicycle paths to connect Crystal City to Long Bridge Park, the Mount Vernon Trail, and the Pentagon.

[15] I-395's turn-off-to-stay-on movement into the 3rd Street Tunnel causes confusion among drivers who intend to continue straight on the Southeast Freeway, but do not realize that they need to follow the posted "Exit 5" for I-695 to do so.

WTOP traffic reporters monitor the area with their own cameras, and note numerous incidents of dangerous weaving, as well as trucks – which may be over-height or prohibited from the tunnel – reversing up the exit ramp to continue on the Southeast Freeway.

[17] In January 2021, the American Association of State Highway and Transportation Officials (AASHTO) approved a request by the District of Columbia to eliminate the entirety of I-695 and renumber it as an extension of I-395.

[18] Although the Federal Highway Administration (FHWA) also approved the request on April 23,[19] DDOT subsequently delayed updating signage in the area.

This prompted renewed pressure on DDOT from the FHWA in September 2023, as both printed and digital maps were beginning to show the long-since-approved but still unsigned designations.

DDOT admitted that work on the re-signing had not started and would take an estimated two to three years, and sought to reduce the increasing confusion caused by updated third-party maps.

However, DDOT pushed the date to fix the problems until 2020 due to the expense and the need to replace or repair several deficient bridges elsewhere in DC.