Police say they received reports of the vehicle travelling northbound on the southbound carriageway between junctions 32 and 33 at around 9.30am on Thursday, March 29.
Lancashire Road Police immediately liaised with Highways England and matrix signs were set to warn drivers of the hazard.
But despite their warning messages, police say drivers ignored the signs and continued to drive as normal.
A spokesman for Lancashire Road Police said in a post to social media: "Vehicle driving the wrong way on the M6 from Lancaster to Preston.
"Despite warning messages of an oncoming vehicle and speed limit restrictions. Vehicles ignored this and continued as normal.
"These messages are not displayed without good reason."
A Highways England spokesman said: "We set the matrix signs to warn drivers to take precautions after we received these reports."
"Police searched the area for the driver who was not found."