SR 240 begins at an intersection with SR 24 west of the Hanford Nuclear Reservation in northwestern Benton County. SR 24 continues west towards Yakima and north across the Hanford Reach of the Columbia River on the Vernita Bridge. SR 240 travels southeasterly along Cold Creek Valley at the foot of the Yakima Ridge and Rattlesnake Hills, forming the boundary between the Saddle Mountain National Wildlife Refuge (part of the Hanford Reach National Monument) and the rest of the Hanford Site, including the Laser Interferometer Gravitational-wave Observatory. Cold Creek empties into the Yakima River near the Horn Rapids Dam, where the highway intersects SR 225, which continues southwest to Benton City.