Loye produced his own version of the reverse-slog which Pietersen thrust into the spotlight with England at the weekend, changing his stance to launch off-spinner Gareth Breese over cover for six with a left-handed sweep.
But Morkel left that in the shade with an astonishing onslaught that shattered Lightning's hopes and also wrecked their unbeaten record in the North Division.
Durham's hopes appeared to be fading fast when Francois Du Plessis had dangerman Phil Mustard caught at cover for 61, leaving them rocking on 127-4 in the 16th over.
Kyle Hogg then tied Morkel down for the first four balls of the next over, leaving Durham needing an improbable 50 to win with only 20 remaining.
But 14 balls later, and the scores were level. Morkel started off by hitting Hogg for consecutive sixes, and then added two more in the next over as Lancashire's gamble of sticking with the occasional leg spin of Du Plessis backfired.
Dominic Cork was recalled for the 19th over but it made no difference as Morkel hit his fifth sixth and Shaun Pollock added another, with a misfield from Sajid Mahmood gifting Durham another boundary to remove any remaining doubts about the outcome.
Bossed
"It's not fair when a bloke is hitting the ball like that - not just over the rope, but 25 rows back," said skipper Stuart Law.
"We bossed the game for 17 overs out in the field but in the end we were undone by some solid batting.
"I can't be too critical of the guys because we played pretty well. The big thing is how we bounce back from this, especially with two games against Yorkshire in the next three days.
"With 10 games in the group this year you're not going to win them all. We would probably have taken three from four although obviously it's disappointing not to have won them all when it looked as though we could have done."
The game had everything, even a couple of doses of controversy. First Lancashire was awarded six bonus runs because Durham failed to bowl their overs quickly enough. Then Loye was involved in a war of words with Mustard after the England keeper survived an appeal for caught behind.
When Mustard was dismissed two overs later, Loye seemed to point him towards the pavilion - and umpire John Holder was less than impressed.
So it was a mixed night for Loye, although he will surely be most delighted by the fact that he has finally shown some form.
He shared a second wicket stand of 77 with Law, who was in majestic form to hit his first Twenty20 half century for two years from only 34 balls.
Steven Croft and Gareth Cross also chipped in late in the innings but Lightning were pegged back by Scott Borthwick, an 18-year-old leg-spinner from Sunderland making his Durham debut who took 3-23 from four impressive overs.
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