Simon Katich completed a double-century as Lancashire assumed control on the third day for their Division Two clash with Northamptonshire at Wantage Road.
The former Australia opener hit 200 from 322 balls as the visitors made 442 all out before reducing their opponents to 123-4 at the start of their second innings.
David Willey's five-wicket haul proved the only real bright spot for Northamptonshire, who are nine runs behind heading into the final day of the top-of-the-table clash.
Lancashire began the day on 262-4 and were given a reprieve when Katich was was dropped by stand-in captain David Sales at second slip while on 115.
Luke Procter was eventually dismissed for 85 when he nudged Andrew Hall's delivery to wicket-keeper David Murphy to end a superb fifth-wicket stand of 145.
Willey then struck when he trapped Lancashire wicketkeeper Gareth Cross (7) lbw before he repeated the trick to Wayne White (1) and knocked Kyle Hogg's off stump over for a duck.
But Katich continued to be the scourge of Northamptonshire by going past 150 after lunch, his ninth-wicket partnership of 128 with captain Glen Chapple setting a new record for Lancashire against their opponents.
Chapple comfortably completed his half-century off 94 deliveries before falling on 57 when he was taken by Hall at slip to give Willey (5-108) the fifth five-wicket haul of his career. Katich was the last man out, falling one ball after bringing up his double-hundred
Northamptonshire began their second innings after tea and lost Kyle Coetzer (10) in the seventh over when Karl Brown took a superb catch low to his right at third slip off the bowling of Chapple.
Sales made it to 30 before playing Simon Kerrigan onto his stumps and the same bowler then dismissed Ben Duckett for 24 when his delivery spun into his off stump. Kerrigan also dismissed Cameron White (1) to leave Northamptonshire in trouble heading into day four.