Fabio Capello's side struggled during the first half before Del Piero, who has been sidelined with an Achilles tendon injury, provided the breakthrough eight minutes after the break.
Brazilian Emerson crossed and Del Piero pounced on Zlatan Ibrahimovic's header down to fire Juve in front.
Del Piero doubled the lead seven minutes later when he drove home a right-foot shot after good work from overlapping full-back Jonathan Zebina.
Although Siena continued to cause Juve some difficulties, Mauro Camoranesi made sure of their sixth win from seven games when he headed home a cross from Del Piero.
The result moves Juventus on to 19 points, with champions Milan on 13 ahead of Sunday's showdown with Inter.
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Giampaolo Pazzini put Atalanta ahead in the second minute taking advantage of a poor clearance from Cagliari's Greek goalkeeper Thoefanis Katergiannakis.
But the Sardinians fought back 10 minutes later when Gianfranco Zola put Mauro Esposito through and the Italy international rounded Atalanta goalkeeper Massimo Taibi before slotting home.
Zola played a part again when the visitors took the lead in the 29th minute, his free kick leading to Simone Loria's goal from close range.
The Bergamo side went in level at the break though after Riccardo Montolivo slotted home following good work from former AC Milan midfielder Demetrio Albertini.
Cagliari were down to 10 men five minutes after the restart when Massimo Brambilla was sent off for a second yellow card but despite plenty of pressure Atalanta could not find a winner.