The collision occurred on the M6 northbound between junctions 35 (Carnforth Interchange) and 36 (Crooklands Interchange) at approximately 6.15am.
A full closure was initiated on the northbound carriageway following the smash, with two lanes also closed on the M6 southbound.
Police confirmed one of the drivers was rushed to hospital with "serious leg injuries" and the closures were "likely to remain on for a considerable time".
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A diversion was put in place until the northbound and southbound carriageways fully reopened at around 2.15pm.
Crews worked to "remove the two lorries, clear away hundreds of plastic water bottles and an oil spillage, and repair damage to the central reservation barrier."
Cumbria Police, Lancashire Police, Cumbria Fire & Rescue, Lancashire Fire & Rescue, North West Ambulance Service and National Highways all attended the incident.
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