The in-form striker bagged a quick-fire first-half brace, taking his league tally for the season to eight, to put Verona in command at Stadio Marc'Antonio Bentegodi.
Substitute Weston McKennie pulled one back with 10 minutes remaining but could not prevent a second loss in the space of four days for the visitors, who were also beaten 2-1 by Sassuolo in midweek.
After a fourth straight home win, Verona moves above Massimiliano Allegri's men on goal difference into eighth place.
Igor Tudor has overseen an upturn in Verona's fortunes since replacing Eusebio Di Francesco in September.
Indeed, no side has since scored more Serie A goals than the Gialloblu, who took the lead after just 11 minutes.
Simeone, who netted four times against Lazio last time out, slotted home after Wojciech Szczesny parried Antonin Barak’s initial effort.
The forward grabbed his second in emphatic fashion just three minutes later, latching on to Darko Lazovic's pass before arrowing a wonderful 25-yard strike into the top corner.
It was the 15th goal Juve had conceded in its opening 11 matches, the first time it has done so during a Serie A season since 1961-1962.
The visitors looked to respond before the break, Alex Sandro drilling into the side-netting while Paulo Dybala clipped the top of the crossbar.
Juventus improved in the second half and pulled a goal back in the 80th minute, McKennie controlling Danilo's fizzed pass before firing home off the underside of the crossbar.
It then took magnificent reflexes from Lorenzo Montipo to deny Dybala later on as Verona held out for another impressive win.