Quetta Gladiators rode on thumping half centuries from Shane Watson and Rilee Rossouw to make it three consecutive wins for their side.
Quetta also continued to top the six-team table as they chased down 161 in 18.3 overs.
The table-toppers were off to another solid start of 39 before opener Ahsan Ali was dismissed off Irfan’s bowling. Watson and Rossouw then took the game away as they stamped their authority on Multan bowlers, adding 56 for the second wicket.
Watson was caught on the fence off Afridi’s bowling but at that point, it was too easy for the Gladiators.
Rossouw raced to his half century off 35 balls as he and Umar Akmal (18-ball 17) added 66 for the third wicket as Multan bowlers looked helpless.
Earlier, Shoaib Malik smashed his second fifty of the tournament while James Vince struck six boundaries in his 17-ball 28 to lift Multan Sultans to 160-8 after they were put into bat first.
Vince was cruel on Mohammad Nawaz, clobbering three boundaries in the fourth over of the innings before the left-arm spinner dismissed him leg-before on DRS.
Opener Shan Masood was undone by a well-disguised googly by Fawad Ahmed but it was Shoaib Malik who had to keep things intact for his side. The skipper, alongside Daniel Christian add 73 for their fourth wicket stand.
Afridi was trapped leg-before for a first-ball duck while Russell was one of three wickets to fall in the last over, smashing three boundaries in 12-ball 18.
Irfan Junior was the pick of the bowlers for Gladiators, taking 2-32 while young Ghulam Mudassar fetched 2-44.