Parts of US 62 follow what once was the Ozark Trail,[1] including the historic bridge across the South Canadian River in Newcastle, Oklahoma[2] (the first structure built with federal highway funds in Oklahoma after lobbying efforts by Stanley Draper).

In Brownfield, US 62 picks up US 82/US 380 from Plains for a four-way concurrency for about two blocks, where US 380 heads east toward Tahoka.

US 62 splits from US 82 and joins with State Highway 114 (SH 114) for approximately 10 miles (16 km) along the campus of Texas Tech University's southern border.

US 62/US 70 then east through Matador to Paducah, and north again dropping off US 70 and gaining US 83 through Childress to a point 17 miles (27 km) to the north of Childress where it turns east alone, before crossing the Texas–Oklahoma border five miles (8.0 km) west of Hollis.

From Anadarko, US 62 runs east through Verden to Chickasha and northeast through Blanchard and then Newcastle before returning to a concurrent route with I-44 into Oklahoma City and then with I-240 and I-35 through much of the city before leaving I-35 at Northeast 23rd Street (exit 130) two miles (3.2 km) east of the Oklahoma State Capitol.

US 62 then leaves I-40 to continue north to Okmulgee and east to Muskogee, and heads northeast through Fort Gibson and Tahlequah and into Arkansas.

In addition to sections of I-44, I-240, I-35 and I-40, US 62 also runs concurrent with other US highways over its miles across Oklahoma including US 281 from Lawton to Anadarko and US 277 from Lawton north about 11 miles (both including the 8-mile (13 km) I-44 concurrency north of Lawton), US 81 in the Chickasha city limits, a second US 277 concurrency from Chickasha to Newcastle, US 75 from Henryetta to Okmulgee, US 64 from an intersection near Taft to Muskogee and US 69 in the Muskogee city limits.

The route passes through several cities and towns, including Fayetteville, Springdale, Bentonville, and Rogers.

US 62 enters Illinois from Missouri by means of a bridge over the Mississippi River, turning east at US 51 with US 51 joining the concurrency.

After passing through Georgetown and Cynthiana it leaves Kentucky in Maysville over the Simon Kenton Memorial Bridge.

In Washington Court House, US 62 meets up with State Route 3 (SR 3) and continues all the way into Columbus, passing through the towns of Mount Sterling, Orient, Harrisburg, and Grove City.

After heading toward downtown Columbus, US 62 diverts from SR 3 onto US 40 (Broad Street) for a few blocks to Nelson Road.

US 62 runs concurrently with I-670 near John Glenn Columbus International Airport until the eastern side of I-270 where US 62 heads toward Gahanna, New Albany, Johnstown, Utica, Millersburg, and Navarre.

The highway passes West Lawn Cemetery and the President William McKinley memorial and tomb in Canton.

US 62 enters New York State from Pennsylvania in Chautauqua County, south of Frewsburg, past which it intersects with I-86 (Southern Tier Expressway).

US 62 briefly overlaps NY 324 (Sheridan Drive) in the town of Amherst, and turns northward as Niagara Falls Boulevard, intersects I-290, then exits Erie County and enters Niagara County, as US 62 crosses the Erie Canal / Tonawanda Creek and travels into the town of Wheatfield.

The northern (eastern) terminus for both US 62 and Business US 62 is at NY 104 (Main Street), less than 2,000 feet (610 m) from the Rainbow Bridge and U.S. Customs.

[9] The measure was sponsored by then Senator William Stachowski, and Assemblyperson Francine Delmonte as proposed by the Sons of the American Legion Post 880 as a way to salute and commemorate the service and sacrifice of all veterans of the US.