Officials said dense fog is likely to blame for the crash. At least 51 people have been hospitalized, with at least eight critically hurt.
The collision happened around 8 a.m. Thanksgiving Day on Interstate 10 near Beaumont, which is about 80 miles east of Houston.
It wasn't immediately clear how the pileup began. Officials said the fog was so thick that deputies didn't immediately realize they were dealing with multiple accidents.
Uninjured drivers tried to help as authorities sorted through the wreckage.
The Associated Press contributed to this report.