The veteran's lethal display of finishing took his tally to five goals in just three games since the new campaign kicked-off - to remind England boss Southgate of what he is missing.
Southgate had travelled to the Etihad to run the rule over the likes of James Maddison, Harvey Barnes, James Justin and Phil Foden before naming his latest squad on Thursday.
But it will have been Vardy dominating his thoughts on the drive home to Harrogate after the 33-year-old provided further proof that he remains the most prolific striker in English football.
Vardy, who retired from international football following the 2018 World Cup but has said he would return if needed, won the Golden Boot last season.
It remains the perfect fit for his golden right foot, which destroyed the former champions as Guardiola saw his side concede five goals in a league game for the first time since he became boss in 2016.
No-one had seen this coming after Riyad Mahrez haunted his former club with a wonder strike inside four minutes to fire City into a deserved lead.
Mahrez was instrumental in helping the Foxes win the title in stunning fashion back in 2016, but he never produced a finish in that historic campaign as spectacular as this one after blazing an unstoppable volley past Kasper Schmeichel and into the top corner of the net.
Brendan Rodgers had started with a back five when his side were defending in a bid to contain the hosts, but his plan hadn't accounted for the brilliance of Mahrez.
Who needs Sergio Aguero and Gabriel Jesus - when Mahrez can do something like this?
Guardiola will be without the striking duo for the next month at least and was forced to select Raheem Sterling in the false nine position here.
The change didn't seem to hinder City, who dominated from the start to pin the Foxes deep inside their own half.
Rodrigo fired a shot just over the crossbar while Fernandinho should have scored from a close range header as the visitors found themselves under siege.
But after weathering the storm the Foxes managed to turn the game completely on its head when Kyle Walker's stupid challenge on Vardy gifted the visitors a penalty on 37 minutes.
Vardy slammed it past Ederson to level matters, before firing his side ahead nine minutes into the second half, meeting Timothy Castagne's cross with a sublime flick that left City's goalkeeper bamboozled.
Guardiola wanted his side to respond - but all he saw was a total collapse that does not bode well for the future.
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City conceded another penalty on 58 minutes when Eric Garcia tripped Vardy, who beat Ederson again to complete his hat-trick.
Substitute Maddison piled on the pain for Guardiola with a brilliant shot into the top corner on 76 minutes before Nathan Ake pulled one back six minutes from time.
But Youri Tielemans rendered it meaningless when converting his side's third spot kick of the afternoon after Benjamin Mendy had felled the impressive Maddison - as City conceded five goals at home for the first time since losing to Leeds in the FA Cup 20 years ago.