It travels north–south through Washington, including long concurrencies with Interstate 82 (I-82) and I-90, and connects the Tri-Cities region to Spokane and the Canadian border at Laurier.

Average 2016 traffic volumes on non-concurrent sections of the highway ranged from a minimum of 380 at the Laurier border crossing to 64,000 on the Blue Bridge between Kennewick and Pasco.

The freeway carrying both highways travels north over the Fallbridge Subdivision of the BNSF Railway system and through an interchange with SR 14 east of Plymouth before traversing Fourmile Canyon.

[10][11] I-82 and US 395 turn north at Bofer Canyon and travel across irrigated farmland before crossing over the Horse Heaven Hills and intersecting SR 397.

[13] The highway continues north onto Ely Street and turns east near the Zintel Creek before crossing over the BNSF Yakima Valley Subdivision and intersecting SR 240 in a dogbone interchange northwest of downtown Kennewick.

[9] The freeway travels along the south side of Tri-Cities Airport and the Columbia Basin College campus and crosses over the BNSF Lakeside Subdivision near a major railyard.

[10][18] At a cloverleaf interchange with SR 397 in northeastern Pasco, US 395 splits from I-182 and travels north onto a divided highway that runs through an industrial area on the east side of the airport and railyard.

[19] The highway traverses an interchange at Kartchner Street before leaving Pasco, traveling northeast into the irrigated farmland of the Columbia Plateau along the BNSF Lakeside Subdivision, which also carries Amtrak's Empire Builder passenger trains.

[12][21] From Ritzville, US 395 runs concurrently with I-90 as the freeway travels northeast through a predominately rural area of Adams and Lincoln counties while following the BNSF Lakeside Subdivision.

The seven-lane highway continues north along a commercial strip surrounded by Spokane's residential neighborhoods and passes the NorthTown Mall before reaching an intersection with SR 291 at Francis Avenue.

[23] US 2 splits from Division Street in the community of Country Homes, while US 395 continues north past the Whitworth University campus to Fairwood.

The divided highway continues for several miles until reaching Hamann Corner on the Half Moon Prairie, which marks the northern extent of Spokane's contiguous suburbs.

[12] The two-lane, undivided highway carrying US 395 continues northwest along the BNSF Kettle Falls Subdivision and passes Deer Park before entering Stevens County.

[10][11] After briefly turning due west in Clayton, US 395 climbs the foothills of the Selkirk Mountains and travels along the east side of Loon Lake before reaching a roundabout with SR 292 at the community of the same name.

The highway leaves the railroad and continues northwest past Deer Lake and several quarries before reaching an intersection with SR 231 on the Colville River.

The highway and the Kettle Falls International Railway travel along the east side of the river valley and pass through the communities of Addy, Arden, and Orin near a section of the Colville National Forest.

It begins a concurrency with SR 20 in downtown Colville, which continues as the highway turns northwest and travels through another roundabout at the north end of the city.

[37] The State Highway Board selected a route closely paralleling the Northern Pacific Railway's Pasco Division over existing county roads.

[49] By 1991, when the Intermodal Surface Transportation Efficiency Act designated US 395 between Reno, Nevada and Canada as a high priority corridor of the National Highway System, and earmarked $54.5 million for improvements in Washington,[50] the portion between Pasco and Mesa had been four-laned.

WSDOT formally opened the last piece, 15 miles (24 km) of new northbound lanes near Lind, on November 21, 1995, completing a four-lane cross section between the Tri-Cities and Spokane.

A major portion of the highway from the US 2 junction to Colville has been realigned and straightened over the years, including sections near Loon Lake, Chewelah, and Arden.

In recent years, a number of changes have been made to address growing traffic issues; including (but not limited to) the addition of left-turn channelization at important intersections, a variety of different paving projects, the construction of two roundabouts in downtown Colville, a truck route that starts and ends at those roundabouts, and the addition of uphill passing lanes in some places.

[citation needed] In the early 1990s, the state government considered rerouting US 395 onto SR 25 in order to direct highway traffic towards Trail, British Columbia, but later abandoned the plan.