Historic Columbia River Highway State Trail web site

"The one-mile section of trail from the Viento campground to the Starvation Creek waterfall is now fully handicapped accessible."  I haven't been yet.

As for the rest, sounds like most of it may not be great in a wheelchair:

"The trail, two disconnected paved ribbons along abandoned stretches of the historic highway, give you more than 10 miles of sightseeing thrills... All segments of [this] trail are rated moderate to difficult for people with disabilities."

The Twin Tunnels section is 5 miles long. "Both trailheads for the Twin Tunnels segment require a day use pass $5 daily day-use fee or buy a 12-month permit for $30 or a 24-month permit for $50. A yellow self-service machine dispenses daily passes at each trailhead. There's a visitor center at the west trailhead with brochures and other information."

"The other open, paved section of the trail parallels Interstate 84 between Cascade Locks and Bonneville Dam (the trail actually extends from Moffett Creek to Cascade Locks)."