The Bayern Munich striker put the Manschaaft ahead in the 13th minute before Michael Ballack doubled the lead in the 25th minute.
Bastian Schweinsteiger added the third for the visitors 11 minutes later but Stanislav Varga pulled one back in the 58th minute.
Podolski was again in the score sheet in the 72nd minute to complete the rout.
The victory placed Germany in second place of Group D with six points and one game in hand, three behind leaders Czech Republic, who tied Republic of Ireland 1-1.
Elsewhere, Robin van Persie inspired Holland to a 2-1 home victory over Albania in Group G action.
The Arsenal striker opened the score in the 15th minute when his close-range shot found its way into the back of the net.
He was the cause of the second goal four minutes before the break when his cross was converted by Albania defender Debatik Curri into his own net before Debatik Curri pulled one back seven minutes past the hour mark.
The result put Holland in second place of their group with seven points on level with leaders Romania.