The freeway travels through the suburb of Tumwater, passing the Olympia Regional Airport and several state office parks before reaching the terminus of US 101, a major highway that encircles the Olympic Peninsula, on the south side of Capitol Lake.

At the Westfield Southcenter shopping mall in Tukwila, I-5 intersects SR 518, the primary means of access to the airport and Burien, and I-405, the eastern freeway bypass of Seattle that travels through Renton and the Eastside.

[39] Mid-way along Beacon Hill near Jefferson Park, the freeway turns due north and intersects the east end of the Spokane Street Viaduct, part of the West Seattle Bridge, which has additional ramps to the SoDo area and the VA Puget Sound Medical Center.

[40] At the north end of SoDo and Beacon Hill, I-5 intersects I-90, the state's major east–west freeway, forming a large interchange with ramps to T-Mobile Park and Lumen Field, two of the city's professional sports stadiums.

The thirteen-lane freeway, among the widest in the United States,[41] runs in the full block between 6th and 7th avenues between downtown to the west and First Hill to the east, home to Harborview Medical Center and Yesler Terrace.

It passes to the east of Seattle's tallest building, the Columbia Center,[42] and the city's Central Library before adding a set of reversible express lanes in the median near Madison Street.

The freeway travels along the north end of Capitol Hill through the Eastlake neighborhood on the east side of Lake Union, passing over the I-5 Colonnade mountain bike park.

[47] At Roanoke Park, I-5 intersects the western terminus of SR 520, a major freeway that crosses Lake Washington on the Evergreen Point Floating Bridge to Bellevue and Redmond.

[25] The heavily trafficked Mercer Street and SR 520 exits use ramps that are on opposite sides of the freeway, causing vehicles to weave across several lanes that contributes to traffic congestion.

A pair of rest areas are situated north of the interchange and are the busiest in the state, serving 2.1 million visitors per year, and is home to a 22-foot-wide (6.7 m) Western red cedar stump that was once hollowed out to allow vehicles to drive through it.

[74][75] To the west of downtown Burlington, the freeway intersects SR 20, a major state highway, in a partial cloverleaf interchange that includes several businesses inside the western loop.

[94][96] During snowstorms and severe cold weather, WSDOT keeps the express lanes open in one direction for the entire day to prevent snow and ice from causing electronic failures in the automated gates.

[111] The highway system, designed with a minimum of four lanes in rural areas and strict grade separation, was approved for limited funding by Congress in 1944 and planned by the Bureau of Public Roads over the following years.

[117] A separate bill in 1953 authorized planning for a toll highway between Tacoma and Everett to replace the nearly-complete Alaskan Way Viaduct and other urban streets with grade crossings and 19 total interchanges.

[112] A few months later, the state supreme court overturned the $194 million authorization (equivalent to $1.67 billion in 2023 dollars)[114] to build the 65-mile (105 km) Tacoma–Everett expressway as a toll road after finding it to be unconstitutional.

The federal contribution under the Interstate Highways program was anticipated to be $165 million (equivalent to $1.42 billion in 2023 dollars),[114] but come in smaller installments that would require more time to complete the freeway project.

[131] The entire US 99 corridor was subsequently assigned the designation of "Interstate 5" in 1957 and the federal government allocated planning funds to begin engineering of the Seattle Freeway,[132] which commanded its own Highway Department division.

[119][133] Washington was the fastest of the three West Coast states to upgrade sections of US 99 to four lanes and partial Interstate standards using new interchanges, with only 15 miles (24 km) of the highway in northern Whatcom County still two-laned by 1959.

[134] Among the first projects to use federal funding from the 1956 act was an upgrade of the Fort Lewis highway to four-lane freeway standards, which opened in September 1957 and included the relocation of the military base's main gate to a new cloverleaf interchange.

[160] The 3-mile (4.8 km) bypass of downtown Everett between 41st Street and the Snohomish River was completed on January 18, 1968;[161] its opening eliminated fourteen traffic lights and included ramps to connect with the Hewitt Avenue Trestle.

[179] The proposal received a mix of strong support and criticism from members of the public, while the city government endorsed the plan with a caveat that right of way along the freeway be reserved for use by rapid transit.

[187] Construction of the freeway through Downtown Seattle was delayed after 100 citizens marched on June 1, 1961, in protest of the "trench" design and sought to add a lidded tunnel with a rooftop park.

[193] Thiry described the freeway's construction as when "Seattle began taking one of its wrong turns and started to lose its identity as a city" and proposed a park lid from Columbia Street to Olive Way along the entire downtown section of I-5.

[250] The program funded several projects to widen and modernize sections of I-5, including new interchanges in Clark County and the extension of HOV lanes in Everett and from Tukwila to Tacoma.

Construction began in September 2005 under a design–build contract, the third in WSDOT's history, and was completed in June 2008 as part of an accelerated timeline to prepare for the 2010 Winter Olympics hosted by Vancouver, British Columbia.

[256] Construction of an HOV lane system through Tacoma, which would also include a new interchange with SR 16 and the Nalley Valley Viaduct, began in 2001 with the replacement of the South 38th Street overpass to accommodate a wider freeway.

[273][274] The 2003 and 2005 gas tax programs also funded improvements to I-5 in areas outside of the central Puget Sound region, including $322 million for lane expansions on a 18-mile (29 km) corridor in Lewis and Thurston counties.

[282] Other parts of the packages funded seismic retrofitting for bridges and overpasses, and the implementation of smart highway technology in 2010 that included variable speed limit signs in the Seattle area.

[294] A demonstration against the U.S. invasion of Cambodia at the University of Washington on May 5, 1970, held in response to the Kent State shootings, culminated in 5,000 protesters marching onto the Ship Canal Bridge en route to Downtown Seattle.

Widening of an eight-mile (13 km) section through the military base and neighboring DuPont to eight lanes began in October 2018 and is planned to be completed in 2025;[313] the project also includes reconstruction of several interchanges and accommodations for the adjacent Point Defiance Bypass railroad corridor.