City police identify the victims as 35-year-old Marcia K. Parra and 15-year-old Keian Padilla.
The two were pronounced dead at the scene of the crash, which occurred about 8 a.m. Wednesday east of the Sonoma Ranch overpass.
Police say the victims were the only occupants of a sedan that was struck by another vehicle that apparently crossed the highway's center divide.
They say the 21-year-old Las Cruces woman driving the other vehicle was ejected after the collision and her vehicle rolled over at least once.
She's been airlifted to University Medical Center of El Paso. Her name and condition aren't immediately available.