The Foxes hitman put Leicester ahead after catching the Blackpool defence sleeping, only for Charlie Adam to pull the Tangerines level with his third goal in as many games shortly after.
But another from Fryatt after the break, which saw him reach his milestone, helped end Blackpool's unbeaten start to the season.
Steve Howard and Martyn Waghorn recovered from hamstring injuries during the international break and made the Leicester squad.
Seasiders midfielder Gary Taylor-Fletcher was ruled out after suffering ankle ligament damage.
Blackpool's midfield closed down well and made life difficult for the home side during the early stages, while midfielder Keith Southern put a shot wide from 20 yards.
Leicester's Dany N'Guessan did not quite catch a shot from distance and American-born goalkeeper Paul Rachubka made a comfortable save, while Howard had a header kept out by the Seasiders stopper.
Southern beat Chris Weale in the Leicester goal with a hooked shot but it came back off the upright - Jason Euell was then denied by a smart stop from the Foxes stopper on the follow-up.
The visitors continued to dominate but Howard should have done better when he headed a Matt Oakley cross wide of the left-hand upright when unmarked inside the box.
City took the lead in the 26th minute when Richie Wellens put his hand on the ball and took a quick free-kick.
He powered it through along the deck and Fryatt, who was level with defender Rob Edwards when he set off, slotted it through Rachubka's legs to put the hosts 1-0 up.
But a lovely move from the visitors saw them pull level in the 31st minute when Adam played a neat one-two with Euell before firing the ball into an empty net with the stranded Weale looking on.
Oakley rattled the post with a powerful free-kick just before the break as they went in level.
City started the second half on the front foot with Wellens and Oakley both pushing up but the first chance fell to Euell who failed with a free header minutes after the interval.
Adam got away with what looked a handball in the 53rd minute before some calamitous defending handed the Foxes their second in the 59th minute.
A mis-kick from Neal Eardley allowed Fryatt to pounce on the ball, round Rachubka and lash home into an empty net.
Fryatt went clean through in the 71st minute as he looked for his hat-trick but was ruled offside, while Howard was off target with another header as the home side clearly dominated the latter stages which just lacked a goal.