U.S. Route 395 (US 395) is a major United States Numbered Highway in the U.S. state of Washington, that includes a long overlap with Interstate 90 (I-90) between Ritzville and Spokane. The southern piece, from I-82 near the Tri-Cities to I-90 near Ritzville, is a high-speed four-lane divided highway. From Spokane to the Canada – United States border at Laurier, US 395 is mostly two lanes, with some wider sections near Spokane, including the under-construction North Spokane Corridor freeway.

The section of US 395 within the state of Washington starts concurrent with I-82 on the Umatilla Bridge, which goes over the Columbia River. From the bridge, the US 395/I-82 freeway goes north and intersects SR 14's eastern terminus before continuing north and spliting from I-82. As US 395 splits, the freeway enters Kennewick, where it intersects SR 240 and crosses the Columbia River on the Blue Bridge.

As the bridge ends, US 395 enters Pasco and joins I-182 and US 12 before exiting north at an interchange with SR 397. From the interchange, US 395 continues north on the eastern side of the Tri-Cities Airport towards Spokane. US 395 goes northeast and intersects numerous state highways, such as SR 17 in Mesa, SR 260 in Connell, SR 26 east of Hatton, and SR 21 east of Lind before joining I-90 south of Ritzville.

While concurrent with I-90, US 395 intersects more highways such as SR 261 south of Ritzville, SR 23 in Sprague, SR 904 in Tyler, SR 902 west of Cheney, SR 904 in Four Lakes, and SR 902 in Hayford before joining US 2 and entering Spokane.

In West Spokane, US 395/I-90/US 2 intersects the northern terminus of US 195 before US 395 and US 2 split from I-90 in Downtown Spokane. US 395 and US 2 stay joined on Division Street through Downtown Spokane where the highway intersects SR 290 and pass Gonzaga University and Washington State University's Spokane branch. After entering the northern section of Spokane, US 395 and US 2 pass the NorthTown Mall and intersect SR 291 before US 395 splits from US 2 and continues north.

From the Division split, US 395 goes north and intersects more highways like SR 292 in Loon Lake, and SR 231 south of Chewelah before joining SR 20 in Colville and continuing west and intersecting SR 25 in Kettle Falls before splitting from SR 20 and going north. From the split, US 395 goes north to Laurier where it reaches the Canada – United States border, continuing as BC 395.

When US 395 was extended southwest from Spokane into Oregon in the 1930s, it followed existing U.S. Highways - US 730 and US 410 - between the state line and Pasco; it was not realigned to the more direct route via Kennewick until 1985. However, the road from Plymouth to Kennewick, cutting off a bend in the Columbia River, had existed (as a county road) since the early days of the state highway system, and was improved by the 1930s. The Washington State Legislature added the roadway to the state highway system in 1943 as part of a Maryhill-Kennewick branch of Primary State Highway 8. (The main route of PSH 8 turned northeast from Maryhill to Buena via US 97.)

As part of the state's first connected state highway system, the Washington State Legislature designated the Central Washington Highway between Pasco and Spokane in 1913. The State Highway Board selected a route closely paralleling the Northern Pacific Railway's Pasco Division over existing county roads. In 1923, by which time the entire road had been improved, the highway became State Road 11 (Primary State Highway 11 after 1937), but retained its name (which was changed to Columbia Basin Highway in 1929). By that time, several routing changes had been made, with the State Highway Board moving the highway east away from the rail line between Eltopia and Connell and between Connell and Lind, and changing the direct northeasterly route from Cheney to Spokane to a northerly route enting at the Sunset Highway (now US 2) near Airway Heights. In the 1930s, US 395 was extended southwest from Spokane along SR 11 to Pasco, where it continued southeast on US 410 (now US 12) and southwest on US 730 into Oregon, both branches of State Road 3. US 10 was moved south between Cle Elum and Spokane in 1940, overlapping US 395 northeast of Ritzville.[citation needed]

Near Spokane, the Geiger Boulevard cutoff was built in about 1945 as a wartime project, improving access to Geiger Field. This included an interchange with Sunset Highway at the Spokane end. This roadway, and the rest of US 395 between Ritzville and Pasco, was replaced by a freeway in the 1950s and 1960s, as part of the project to turn US 10 into Interstate 90. The first section to open was the bypass of Ritzville to Tokio in the late 1950s, and the final piece was between Tokio and Tyler in the late 1960s. When the bypass of Cheney opened on November 18, 1966, the old route became a short-lived Secondary State Highway 11H, always signed as State Route 904.

As the first phase of converting US 395 between Pasco and Ritzville into a limited-access highway, the Department of Highways constructed a new a two-lane alignment between Connell and east of Lind in the mid-1950s, bypassing Lind and Foulkes Roads northeast from Connell and Wahl Road south from Lind. Another relocation was built in about 1980, moving the highway alongside the rail line between Eltopia and Connell. The southernmost 7.5 miles (12 km) of SR 17, from Eltopia to Mesa, were absorbed into the realignment; SR 17's mileposts now begin at about 7.5. 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, the portion between Pasco and Mesa had been four-laned. That year, the state began an $83 million project, including $10.4 million more from the federal government, to widen the remainder north to Ritzville from two to four lanes. Several interchanges were also added to the road, then one of the state's most dangerous highways. 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. The speed limit was subsequently raised from 55 to 70 miles per hour (90 to 115 km/h) in July 1996, based on road conditions and actual driving speed.

Before the reconfiguration of 2nd and 3rd Avenues in 1951, the original routing of US 395 in Spokane ran northbound on Monroe Street for several miles, crossing the Monroe Street Bridge at Spokane Falls. After turning right onto Garland Avenue, the highway proceeded on North Wall Street, Waikiki Road, Mill Road, Dartford Drive (to late 1940s), and finally North Lane (which was closed for many decades after being decommissioned) before merging with modern-day US 395 a few miles north of Spokane. From the late 1940s to late 1990s, US 395 used the bridge over the Little Spokane River at Wandermere. A new bridge was constructed about 250 feet to the west in anticipation of the North Spokane Corridor, while the old one became part of Wandermere Road. This is the second replacement bridge for US 395 over the Little Spokane River, each one built substantially higher above the water than the previous. (The Little Spokane is at the botttom of a river valley over 300 feet deep.)

The southern end of the highway was moved up to the intersection of Sprague and Monroe in 1930 while the entire highway was shifted east onto Division Street (US 2) in 1937. Sometime in the 1950s, the southbound lanes were relocated to Browne Street, which is immediately due south of the Spokane River.

US 395 through Spokane will be completely transformed by the North Spokane Corridor, an under-construction freeway which intends to address and alleviate a major chokepoint along the state highway system in metropolitan Spokane. The maximum speed limit along the entire route will be 60 miles per hour.

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. The largest bypass was that of Loon Lake, which was built in 1957. Another bypass circumvented Old US 395 around Springdale. That highway eventually became SR 231 while its spur was officially dubbed SR 292. Further north near the town of Arden, a new highway section was built that paralleled the Old Arden Highway, which is now used mostly by local traffic. The last leg of US 395, from Colville to the Canada – United States border, has maintained almost exactly the same alignment since it was originally built. A pair of bridges linking Stevens County to Ferry County, known as the Kettle Falls Bridges, were constructed in 1941 in the vicinity of Kettle Falls over the Columbia River. After passing through some dense forest, the highway finally ends its journey at the border station in Laurier; where the highway transitions itself onto British Columbia Highway 395. 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, and the addition of uphill passing lanes in some places.