The Kansas Highway Patrol reported a 2016 Ford F150 driven by Andrew L. Manning, 34, Wichita, was westbound in the eastbound lane of U.S. 54 eight miles north of Minneola.
The pickup hit a semi head-on. Both vehicles came to rest on the south shoulder of the highway.
Manning and a passenger Ashiona J. Hollingsworth, 27, Winfield, were pronounced dead at the scene.
The semi driver James J. Kopp, 72, and Tommy L. Wilkie, 48, both from Minnesota were transported to the hospital in Minneola.