Chasing their victory target of 176, Lancashire resumed their innings on 132-3 with Shivnarine Chanderpaul and Liam Livingstone at the crease.
It took less than six overs for the pair to get the runs required, as Chanderpaul struck successive sixes followed by a four from Scott Borthwick to finish the match in comprehensive fashion.
He finished unbeaten on 43 from 44 balls while Livingstone made 69.
It is the first time since 2000 that Lancashire have won four matches at Old Trafford in a single County Championship season, with all five of their wins – including one at Southport – coming at home.
The second-placed finish represents Lancashire’s highest placing since clinching the Division One title in 2011.
They finished 72 points adrift of leaders Essex.
Surrey finish third, a further 13 points behind Lancashire.
Red Rose head coach Glen Chapple said: “It was identified as a difficult division this year and I don’t think it’s panned out the way that people thought.
“We have to be pleased with our efforts and how we’ve played and delighted with the lads work ethic.
“We have to be hungry to improve, ultimately all teams especially this club want to win trophies.
“All in all we walk away happy with our efforts and looking to get better all the time.
“We have to be very pleased with our development of players.
“Our top four is full of young home-grown players. We have done both development and performances this year and hopefully that will continue next season.
“This year I felt we’ve been the strongest we’ve been for many years in terms of getting up to a good start as well as backing up from a tricky one.
“From this season we can look at our away form, because we’ve won five games and home and we’ve won five games in total. We’ve lost on three pitches that were results pictures and we were ever so slightly outbowled.”