The crash happened around 2:30am in the 12700 block of U.S. 59 North.
According to police, Sheila Cronk and Justin Springer were in both town from Lincoln, Nebraska and Cronk was driving a Ford Focus rental car.
The Focus was northbound on U.S. 59. A Jeep, driven by a 45-year-old Houston man, was going the wrong way and struck the car head-on, officials said.
The driver of the Jeep was taken to Memorial Hermann Hospital in unknown condition.
Cronk and Springer both died at the scene. They were both in their 20s, officials said.
Sugar Land and Stafford Police Departments are investigating the crash. They have not yet determined whether alcohol was a factor.