The Outlaws restricted the Lightning to a below par 216 for eight having invited them to bat on a testing but far from impossible batting surface.
Karl Brown top-scored for the hosts with 77 off 114 balls, but Samit Patel’s three for 31 from five overs of left-arm spin was central to a late innings stumble.
Seamer Gavin Griffiths and off-spinner Arron Lilley then shared five wickets as Notts slipped to 146 for six in the 35th over of their chase, including James Taylor for 56 off 77 - his third successive fifty.
But their heroes were seventh-wicket pair Chris Read and Brett Hutton, who hit 47 not out and 33 not out respectively and shared 71 in 12 overs to seal the two points.
Earlier, Lancashire lost five for 42 to slip from 162 for three in the 42nd over, with Jake Ball also taking two for 24 from eight.
The Lightning were on course for 240 or 250 with Brown and captain Steven Croft in partnership for the fourth wicket. They shared 66 in 15 overs before departing in successive Patel overs.
Patel only came into the attack to bowl the 38th over and had Brown stumped in the 42nd and Croft caught at deep square-leg in the 44th. He later had James Faulkner caught behind off a top-edge.
Aside from giving Brown two lives on five and 39, Notts’ catching was impressive.
Notts lost openers Riki Wessels and Alex Hales (32), as well as Brendan Taylor, inside eleven overs of their chase to 21-year-old Griffiths, leaving the score at 53 for three.
Wessels was caught at deep backward square-leg in the seventh over, Griffiths’ first, before Hales was brilliantly caught and bowled one-handed and Taylor caught at mid-off in the space of three balls in the eleventh.
James Taylor and Patel (29) shared 51 inside 12 overs to steady the ship before the latter found deep mid-wicket off Stephen Parry’s left-arm spin in the 23rd over.
The target became double figures in the 28th with Taylor closing in on his half-century.
When Lilley had Steven Mullaney caught at leg slip in the 31st and Taylor stumped in the 35th, Notts were six down and still 71 short of their target.
Read and Hutton, however, calmly saw their side home with a little over three overs to spare.
Lancashire have now lost three of their first five matches in this competition and realistically need to win their last three to have any hopes of progressing through to the last eight.