CFD said the crash happened on Highway 231 near Country Road 2243 before noon.
Officials said the 18-wheelers were carrying hazardous materials. The other two vehicles involved were pickup trucks.
Details on how the crash happened or what caused it are limited.
SkyEye flew over the scene, where two heavily damaged pickup trucks were seen sandwiched between the two semis.
CFD said HCA Air Life transported two people, and the others were taken by ambulance. It remains unclear how many people were involved or injured.
The Harris County hazmat unit was called to the scene to clear the tanks on the 18-wheelers. The Texas Department of Public Safety said they are investigating the crash.