After a bright start, the Foxes collapsed from 88-1 in the 10th over to be all out for a disappointing 142 in the 20th after Lancashire had won the toss and put them in.
Skipper Liam Livingstone, who made an explosive 100 off 51 balls in Lightning’s nine-wicket win at Derbyshire earlier in the competition, starred with the ball this time, claiming 4-17 from his four overs of off-spin.
He and leg-spinner Matty Parkinson between them claimed 5-39 from eight overs as the Foxes were well and truly shackled, hitting only one boundary between the 10th over and the 17th and losing six wickets in the process.
Livingstone then smashed the first three balls he faced for four off Pakistan strike bowler Mohammad Abbas on the way to 28 off 11 deliveries to give his side a flying start in pursuit of their target.
Dropped twice as he swung at everything, the 24-year-old all-rounder was eventually caught by Mohammad Nabi at mid-on – who had put him down off the previous ball – off Ben Raine.
After closing the PowerPlay on 68-1 Lightning lost Arron Lilley for a 12-ball 19 when Matt Parkinson’s twin brother Callum came into the Foxes attack but the league leaders never looked in any danger of falling short of their target.
Opener Alex Davies (51) and England’s Keaton Jennings (37) were able to ease them over the line with 20 balls to spare thanks to an unbroken partnership of 70.
Livingstone said: “It was a good night for us. We set out our stall to play aggressive cricket and we’ve done that tonight, taking wickets at key times and taking the attack to them with the bat.
“We thought their score was under par but we knew the Powerplay was vital, so it was one of those where you go as hard as you can and on this occasion it worked for us.
“I wasn’t expecting to bowl too much but sometimes it is your day and it was nice to contribute with the ball.
“It feels like we are building a bit of momentum. We have proved we are a very good white-ball team at the moment but you have to perform in the middle and it will be a tough game for us against Yorkshire on Friday night.
“Everyone is very excited about that game and hopefully we can carry on doing what we are doing.”