The highway turns west and follows the Columbia River upstream, passing a public boat launch and a campground within the Saddle Mountain National Wildlife Refuge.

[2] As the terrain transitions from brushland and sand dunes to irrigated farmland,[3] SR 243 turns northwest and passes the Priest Rapids Dam and Wanapum Heritage Center at the south end of Desert Aire,[4] a resort town with its own golf course and public airport.

[7] North of Mattawa, the bluffs of the Saddle Mountains cause the river and its valley to narrow, leaving SR 243 to run directly on the eastern bank as it traverses the Sentinel Gap.

[11] A road following the un-dammed Columbia River from the Priest Rapids to Vantage was built by the early 1910s, roughly along the path of modern SR 243.

[15] Construction on the highway began later in the year and was completed in the early 1960s,[16][17] shortly before the opening of the Vernita Bridge at its southern terminus with SSH 11A.