The forward side-footed in a Daniele Mannini cross in the 72nd minute after a slip-up by Inter full back Davide Santon to give the Genoa side a home win and 15 points from six games.
Inter are in second spot two points further back and alongside Fiorentina after they won 1-0 at Livorno with a 76th-minute penalty by Stevan Jovetic.
Inter came close with a powerful Samuel Eto'o shot shortly before Pazzini struck but the champions could have few complaints about their first league defeat this term.
"It was a very important goal in front of this full house," Pazzini told Sky television. "We're top. It's a great night."
"We picked ourselves up immediately after Florence," he added, referring to Wednesday's 2-0 defeat at Fiorentina that ended a run of four wins.
Samp midfielder Angelo Palombo fluffed the best chance of an intense first half after an Antonio Cassano cross created mayhem in the middle of the box.
Cassano, snubbed by Inter when they were searching for a playmaker in the close season, also had a good opportunity in the 39th minute but bizarrely he went to ground instead of going for goal having skipped past Lucio, getting himself booked.
Inter substitute Ricardo Quaresma had an equaliser disallowed for offside and Samp keeper Luca Castellazzi produced a fine save to keep out a Lucio free kick in injury time.
Fiorentina share second place with Juve and Inter after they put aside the turmoil caused by president Andrea Della Valle quitting this week to beat struggling Tuscan rivals Livorno.
The spot-kick was awarded for a foul by Marcus Diniz on Italy forward Alberto Gilardino, who will be suspended for Fiorentina's big Champions League clash against Liverpool on Tuesday.
The Florence side had to cling on for victory after having Dario Dainelli sent off for a second yellow card in the closing stages.
