The route is the main access road to parts of Auburn, Dryden, Newark Valley and Port Byron.

The road heads northeastward as a two-lane highway, paralleling Owego Creek as it proceeds along the base of a valley surrounding the waterway.

The Tioga County portion of NY 38 passes through mostly rural, forested areas with only small, scattered pockets of development.

NY 38 does not enter the community; instead, it bypasses it to the southeast and follows the eastern branch of Owego Creek into the town of Newark Valley.

The route continues into the small village as South Main Street and passes by several blocks of homes and commercial buildings.

As a result, NY 38 continues through the village limits but passes very few buildings before seamlessly exiting the community and entering another rural area.

The route continues on through the narrowing creek valley into the town of Richford and the hamlet of the same name, where it meets NY 79 in the community's center.

After Richford, the valley continues to narrow for just under 1.5 miles (2.4 km) before reversing course as the route heads into Cortland County and the town of Harford.

[citation needed] Upon entering the border town of Dryden, NY 38 emerges from the valley and becomes Dryden–Harford Road as it heads northwestward through a more low-lying but still undeveloped area.

It remains on Freeville Road until Railroad Street, where it turns west and proceeds into the densely populated village center.

[4] NY 38 proceeds out of Freeville, passing over Fall Creek and heading north along Groton Road through a lightly populated area of the town of Dryden.

The route passes by a mixture of open fields, forests, and isolated homes on its way to the Dryden–Groton town line, where it meets the southern terminus of NY 34B southeast of the hamlet of Peruville.

Now known as Locke Road, NY 38 heads the northwest through another rural, largely undeveloped area into Cayuga County.

[4] Cayuga County, located in the Finger Lakes region of New York, has a highly unorthodox shape.

[5] The route heads northwest from the county line, following the Owasco Inlet through open fields and past small patches of trees to the large hamlet of Locke.

North of the community, the highway crosses over the Owasco Inlet and enters another rural area dominated by fields situated amongst forests.

Once in Fleming, NY 38 runs along the lakeshore and serves a long line of lakeside homes as it passes by a series of fields to the west.

[5] Now in the town of Throop, NY 38 follows the Owasco Outlet through open, mostly flat areas dotted with houses amongst fields and trees.

Within Throop, it serves the small hamlet of Sawyers Corners, where NY 38 meets Turnpike Road (County Route 10B or CR 10B).

The route crosses over the New York State Thruway (I-90) as it leaves the village limits and heads north into a largely undeveloped area of forests and fields.

The route heads through mostly desolate surroundings to the hamlet of Victory, a slightly larger community centered on NY 38.

On April 13, 1819, the New York State Legislature passed a law incorporating the Cortland and Owego Turnpike Company.

They were tasked with connecting Moravia to Auburn by way of a plank road along the western side of Owasco Lake (now NY 38).

[15] The overlap was extended slightly along Southside Drive to NY 17 exit 64 in the 1960s following the construction of the Southern Tier Expressway through the area.