North of Interstate 695 (I-695), the state highway parallels I-83 and serves the suburban communities of Lutherville, Timonium, Cockeysville, and Hunt Valley.

MD 45 begins at an intersection with US 1/US 40 Truck (North Avenue) at the northwest corner of Green Mount Cemetery in Baltimore.

In the center of the county seat adjacent to the Towson Town Center shopping mall, MD 45 passes through the racetrack-shaped Towson Roundabout, where the state highway meets the southern end of MD 146 (Dulaney Valley Road) and east–west Joppa Road.

MD 45 heads northwest from the roundabout, becoming four lanes again, and meets the northern end of MD 45 Bypass (Bosley Avenue) before it gains a center left-turn lane and passes east of the George Washington Carver Center for Arts and Technology.

The route has a partial cloverleaf interchange with I-695 (Baltimore Beltway), at which point it is a four-lane divided highway.

The industrial parks continue past Warren Road in Cockeysville, where the highway crosses Beaver Dam Run.

In Parkton, MD 45 intersects Middletown Road and passes over the Torrey C. Brown Rail Trail and Little Gunpowder Falls.

The roadway continues north as SR 3001 (Susquehanna Trail), an unsigned quadrant route, toward the borough of Shrewsbury.

[7] The first section of the old turnpike to be resurfaced with a 14-foot (4.3 m) wide macadam surface was from Washington Avenue just north of the center of Towson and the hamlet of Texas south of Cockeysville in 1913.

The highway from the contemporary northern city limit of Baltimore near 42nd Street to Washington Avenue just north of the center of Towson was surfaced with bituminous concrete in 1914.

[9][14][15] Other bridges included grade separations at the crossings of the Northern Central Railway at Cockeysville and Parkton built around 1930.

[20][22] When the final section of the US 111 freeway was completed between Hereford and Parkton in 1960, MD 45 was assigned to the stretch of York Road between those communities.

[20][23] US 111 and I-83 were co-signed on the freeway between Towson and Harrisburg until US 111 was decommissioned in 1963; the MD 45 designation was extended south into Baltimore to US 1 at that time.

The four- to six-lane divided highway runs 0.9 miles (1.4 km) along the west side of downtown Towson.

[25] MD 45 Bypass is a part of the National Highway System as a principal arterial for its entire length.