Portions of the highway, including the Fort McHenry Tunnel and the Millard E. Tydings Memorial Bridge, are tolled.

From the Woodrow Wilson Bridge to the community of College Park, it follows a portion of the Capital Beltway, completed in 1964 and numbered as I-95 in 1977.

Prior to 1977, the route was intended to go on a new highway through Washington, D.C.; however, public opposition caused the cancelation of I-95 inside of the Capital Beltway.

A rebuild of this section was begun in 2006, and is underway; as of 2022[update], several miles of express toll lanes have been added to I-95 north of Baltimore, with further widening of the roadway planned through to the Delaware state line.

From Alexandria, Virginia, the roadways, five lanes in either direction, travel together over the Potomac River on the Woodrow Wilson Bridge, briefly cross the southern tip of the District of Columbia (over water), and touch down in Prince George's County west of Forest Heights.

North of the MD 216 interchange, the route encounters its first rest area in the state of Maryland, with separate facilities for the northbound and southbound lanes.

Before its collapse in March 2024, northbound traffic not authorized to make use of either of the direct (tunnel) routes through Baltimore (such as vehicles either carrying hazardous materials or exceeding the tunnel clearance heights) was encouraged to use the eastern half of I-695, which crossed the Patapsco River via the Francis Scott Key Bridge; it is now detoured onto the western half of the beltway, with I-95 being available to all other through traffic.

The tunnel, containing eight lanes, curves underneath the Northwest Harbor and emerges in the Canton neighborhood of Baltimore, quickly encountering the all-electronic toll plaza and connector ramps that lead to and from Keith Avenue.

Starting out eight lanes wide at the junction with I-895, after three miles (4.8 km), I-95 once again intersects with I-695 in Rosedale at what was a unique double-crossover interchange.

As part of the upgrades to I-95 to accommodate express toll lanes in this area, this interchange was replaced with a more conventional four-level stack; all exits are now on the right, and I-95's carriageways no longer cross over one another; a similar project also eliminated the crossovers on I-695.

Just beyond the MD 543 interchange, I-95's carriageways split apart to provide space for the Maryland House service area accessible from both directions.

South of Susquehanna State Park, I-95 encounters the southern end of the remaining tolled portion of the highway at the MD 155 interchange, providing access to Havre de Grace and US 40.

The bridge crosses between bluffs high above the river valley, and is posted with warning signs: "Subject to Crosswinds".

At the northern end of the plaza is exit 93 for MD 222 in Perryville, before continuing through Cecil County toward the Delaware state line.

The "North East Rising Sun" exit off I-95 has been read by some drivers, including children's writer Katherine Paterson, as referring to a single exotically named location.

[12][13] Under the original plans for I-95 in Maryland, the route would not have followed the eastern half of the Capital Beltway from the Woodrow Wilson Bridge to the College Park Interchange.

The Southwest Expressway would have cut through Federal Hill and crossed the Inner Harbor on a fixed bridge with 50 feet (15 m) of vertical navigational clearance.

The highway would have junctioned I-70N a mile (1.6 km) to the northwest of the Inner Harbor, near the eastern terminus of the now-defunct I-170; it would have met I-83 in the northeastern corner of the CBD.

By 1974, I-95 was under construction in East Baltimore between its current merge with I-895 south to a partial cloverleaf interchange with MD 150 (Eastern Avenue).

[15] Despite the route's inclusion in the Interstate Highway System in the mid-1950s, the construction of the Baltimore and Capital beltways had diverted most of the state funds that would have been used to build it.

As a result, both the Northeast Expressway and Delaware Turnpike were renamed the John F. Kennedy Memorial Highway in his honor in December 1963.

To allow a seamless connection between the John F. Kennedy Memorial Highway and the then-unnumbered Harbor Tunnel Thruway, a partial interchange was constructed for I-95 to continue south into Baltimore.

However, this meant that I-95 had to enter from and exit to the right, as evidenced by a southbound flyover ramp; a construction project corrected the problem in 2009 so that I-95 would proceed straight through the interchange.

Construction of the I-95 express toll lanes was part of the $1.1-billion (equivalent to $1.39 billion in 2023[16]) I-95 Improvement Project, which included $756 million (equivalent to $958 million in 2023[16]) in highway and safety improvements along eight miles (13 km) of I-95 from the I-895 interchange to just north of White Marsh Boulevard (MD 43) in northeast Baltimore.

[25] The College Park Interchange was modified in late 1986 to allow free movement along the transition from the I-95 corridor and the Capital Beltway without requiring the use of exit ramps.

Due to the heavy use of this route by commuters and through traffic, the MDTA has begun the process of significantly expanding the highway to increase its capacity.

The expansion plans are divided into short, individual sections; in 2001, the MDTA began public studies to determine the best way to expand the highway to meet current and future needs.

[citation needed] Section 100 is an eight-mile (13 km) segment of the John F. Kennedy Memorial Highway that runs between exit 62 (I-895) and milepost 70.

[35] The reconstruction of the MD 152 interchange had the Old Mountain Road bridge demolished and will relocate the park-and-ride lot just south of the older facility and will be accessed through a roundabout.

[citation needed] The MDTA, at the request of an assortment of elected officials,[36] completed a study which examined a relocation of the northbound toll barrier, which is currently just north of the Millard E. Tydings Memorial Bridge crossing of the Susquehanna River at Perryville.