It happened just before 1 a.m. near Manchester Street near the Houston Ship Channel Bridge.
The driver of an 18-wheeler was northbound on the loop when he tried to avoid two cars that had stopped in the main lanes, witnesses said.
The rig rolled over onto its side as it swerved, causing a big mess on the road.
The driver was taken to a hospital with injuries, but the extent of those injuries wasn't known.
The truck's trailer was loaded with frozen food, authorities said.
Most of the northbound lanes and the shoulder were blocked Wednesday morning, leading to miles of backups along the East Loop.
The crash is now cleared.
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