A master class from Dale Benkenstein and a mature knock from Ben Stokes saw the rack up a partnership of 331 having batted through the first session with little trouble from the Lancashire attack.
Benkenstein reached his hundred off 169 balls, which included 11 fours and the pair pushed Durham past the 300 mark before the end of the first session.
Just as he had done with his hundred the day before, Stokes notched up his 150 just a few deliveries before the end of the session having faced 239 balls and striking 17 boundaries.
At lunch Durham were 403-3 with Stokes 150* and Benkenstein 133*.
A lead of over 100 was established before Benkenstein returned to the pavilion to a standing ovation having been caught behind off Procter for 137.
Stokes hit two huge sixes, including one over the pavilion, a feat that has only been achieved once before, before Lancashire were finally able to dismiss him when he tried to sweep another Croft delivery but instead was bowled for 185, his highest first class score.
Durham were 476-6 once Ian Blackwell was bowled by Kyle Hogg for 21 which brought Scott Borthwick to the crease to join Phil Mustard.
Borthwick added six runs to the total before he was caught by Paul Horton in the slips becoming Glenn Chapple’s second victim of the innings.
A fifty partnership from Mustard and Callum Thorp and a rapid 44 ball half century, which included two fours and three huge sixes from the skipper.
Thorp was dismissed just before tea when he was caught behind off Smith for 22. Durham didn’t declare during the break and returned to the field with 568-8 with Claydon 7* and Mustard 55*.
Claydon was bowled by Keedy for 18 and Mustard was the final wicket to fall when he was caught by Hogg at leg slip off the same bowler for 61.
Durham posted a first innings total of 586 and Lancashire started their second innings trailing by 273.
The home side dismissed the first Lancashire opener in the seventh over, with Steven Moore trapped lbw by Graham Onions for 10.
Thorp claimed the second scalp when Brown was trapped lbw on six with Lancashire 30-2.
Six overs before the end Stokes left the field after attempting to stop a four at point, it was later confirmed that he had dislocated his finger.
Paul Horton and Mark Chilton had steadied the innings and it looked like there were going to be there until the end but a second wicket for Onions saw Horton caught behind for 34.
At the close Lancashire were 69-3, trailing by 204, with Keedy and Chilton set to resume on day four.