I-395 also serves as the southern terminus of Martin Luther King Jr. Boulevard, an urban arterial that provides a western bypass of Downtown Baltimore and connects I-95 with U.S. Route 40 (US 40), US 1, and I-83.

I-395, which carries six lanes, passes to the west of the Federal Hill neighborhood and to the east of M&T Bank Stadium and begins to parallel Maryland Transit Administration's Baltimore Light RailLink and CSX Transportation's Baltimore Terminal Subdivision railroad line, which carries MARC Train's Camden Line.

Each direction of Martin Luther King Jr. Boulevard receives a ramp from northbound Russell Street before it crosses over the state highway.

The highway veers north at Lombard Street and passes along Old Saint Paul's Cemetery, which is adjacent to the University of Maryland, Baltimore, campus.

Martin Luther King Jr. Boulevard has intersections with Franklin and Mulberry streets, which act as the ramps of a diamond interchange with a short freeway segment of US 40 that was formerly I-170.

Martin Luther King Jr. Boulevard has intersections with Druid Hill Avenue and McCulloh Street, which form the southbound and northbound directions, respectively, of Maryland Route 129 (MD 129).

The boulevard continues one more block to its official northern terminus next to the Joseph Meyerhoff Symphony Hall; this intersection's west leg is an east-heading disjoint segment of Park Avenue and its east leg is one-way eastbound Biddle Street (which is paired with the westbound-running Preston Street in this area).

The arterial follows Mount Royal Avenue northwest, intersects the light rail at-grade, crosses over Howard Street, and passes along the northeast side of the Bolton Hill neighborhood.

[7] North of here, Mount Royal Terrace runs one way alongside the southbound side of I-83, between Druid Park Lake Drive and North Avenue; it is complemented by a northbound collector-distributor road on I-83 that connects to eastbound 28th Street and westbound Druid Park Lake Drive.