In the mid-1920s, the section of modern US 20A from East Aurora to Lakeville was part of New York State Route 35 (NY 35).

US 20 was realigned onto its current alignment between Hamburg and Avon c. 1938, and US 20A was assigned to US 20's former routing west of Lakeville and all of NY 254 by the following year.

The route heads east through the Buffalo suburbs on Big Tree Road, entering the town of Orchard Park and passing south of the southern campus of SUNY Erie.

[citation needed] Outside of the village, US 20A becomes Quaker Road, passing through slightly less developed areas as it progresses eastward.

The three routes come together, becoming Main Street and passing by the Fillmore House as it proceeds through the center of the village.

In Wales Center itself, US 20A intersects Four Rod Road,[citation needed] once designated as NY 358[5] and now part of CR 356.

[citation needed] The route ascends approximately 300 feet (91 m),[6] passing under the Rochester and Southern Railroad (RSR)—which runs along the foot of the gorge—before exiting the valley and returning to an east–west alignment as it heads toward Perry and points east.

[citation needed] All oversize trucks are prohibited from using the section of US 20A between NY 19 and Minor Road at the top of the valley due to the steep grade of the hill and the sharp curve at the bottom.

The portion of US 20A in Perry is otherwise uneventful, and the route quietly passes into the Livingston County town of Leicester 2.5 miles (4.0 km) later.

The routes pass in and out of Cuylerville and head eastward into a wide valley, crossing Beards Creek and the Genesee River.

After just one block, the US 20A/NY 39 overlap comes to an end as NY 39 follows Main Street north out of Geneseo toward Avon.

Past the expressway, US 20A continues on a northeast alignment—albeit more eastern than northern—as it intersects NY 256 and enters both the town of Livonia and the hamlet of Lakeville.

[citation needed] As Big Tree Road once more, US 20A acts as the major east–west thoroughfare for Lakeville, connecting the hamlet to I-390 in the west to the village of Livonia to the east.

The two routes converge on Big Tree Road, following the roadway around the northern tip of Conesus Lake and southeastward through the rural landscape between Lakeville and Livonia.

Here, US 20A breaks from NY 15A and continues east on Honeoye Road into the Ontario County town of Richmond.

[citation needed] About 2.5 miles (4.0 km) into the sparsely developed town, US 20A reconnects to Big Tree Road at Curtis Corner.

It leaves the hamlet soon after, turning to the northeast and traversing a series of small hills as it passes into the town of Bristol as Honeoye Road once again.

The portion of what is now US 20A between Four Rod Road in Wales and NY 98 in Sheldon was included in Route 19, a highway that extended from Buffalo to Batavia.

[3][18] On the morning of March 12, 1994, a large section of the roof in the southern end of the Retsof Salt Mine collapsed.

Over the next few weeks, two large sinkholes opened on the surface above the mine, one of them located just south of the US 20A bridge over Beards Creek.

[21] No construction was done on the area for a number of years while a court battle was fought over whether Retsof should reimburse the New York State Department of Transportation to fix the road.

The designation is in memory of Buffalo native Tim Russert, the long-time host of NBC's Meet the Press who died on June 13, 2008.