PA 441 heads out of Washington Boro and runs northwest through wooded areas with some homes alongside the railroad tracks and the river.

[2][3] The route passes through a small section of West Hempfield Township before it enters the borough of Columbia, where the name becomes South Front Street.

The road narrows to two lanes and heads into forests as it passes to the east of Chickies Rock County Park, curving to the northwest.

[2][3] PA 441 crosses the Chiques Creek near the community of Chickies and becomes the border between the borough of Marietta to the southwest and East Donegal Township to the northeast.

The road fully enters East Donegal Township and curves west through residential and commercial areas with some fields, bypassing Marietta to the north.

PA 441 runs through farmland and crosses into Conoy Township, where it heads through a mix of farms and woods with some homes, passing to the north of a Reworld waste-to-energy plant, and curves north-northwest.

[2][3] The route crosses Conoy Creek and runs through the eastern part of the residential community of Bainbridge, turning northwest into farmland to intersect the southern terminus of PA 241.

The road continues northwest through a mix of fields and woods with some homes, becoming closely parallel with Norfolk Southern's Royalton Branch railroad line.

PA 441 and the railroad line curve north and the route heads through the residential community of Falmouth a short distance to the east of the Susquehanna River.

[2][3] PA 441 crosses the Conewago Creek into Londonderry Township in Dauphin County and continues north between farmland and some woods to the east and the Norfolk Southern Royalton Branch and the Susquehanna River to the west.

The route becomes parallel to Amtrak's Keystone Corridor railroad line to the east and crosses the Swatara Creek into the borough of Middletown.

The road passes north of Middletown Area High School and winds northwest through a mix of farm fields and woods with some homes.

Past this, PA 441 turns southeast onto Eisenhower Boulevard, a three-lane road with a center left-turn lane that passes businesses.

The route turns west onto two-lane undivided Highland Street and passes through fields before it comes to the residential community of Oberlin.

[2][4] PA 441 turns northwest onto North Harrisburg Street and heads past more homes, running through the community of Oberlin Gardens.

PA 441 continues past businesses and comes to its northern terminus at an intersection with SR 3010 (Paxton Street) to the east of the Harrisburg city line.

[11][12][13] In the 1950s, the route was shifted west to a straight alignment between Columbia and Marietta instead of bending east along what is now Old Chickies Hill Road.