In an unannounced but already scheduled visit, Panetta landed in southern Afghanistan at the Camp Bastion military base. The trip comes in the wake of Sunday's shooting spree that left 16 Afghans dead, most of them women and children.
Tensions were running high a day after suspected Taliban insurgents opened fire on an Afghan government delegation attending a memorial service for the civilians who were murdered.
The hail of gunfire left one member of the Afghan security forces dead and one policeman wounded.
Panetta was due to meet President Hamid Karzai and local leaders in the south in a bid to reassure Afghans after Sunday's horrific violence when a US Army sergeant allegedly went house to house killing Afghans in the Panjwayi district of southern Kandahar province.
The shooting marked the latest in a string of damaging incidents that have raised questions about the NATO war effort, including the burning of Korans at an American base that triggered violent unrest in which around 40 people were killed.
Panetta's visit coincides with a growing debate in Washington about the course of the 10-year-old war, with some sceptics in and outside the White House arguing for an accelerated drawdown of troops.
Under current plans, the United States aims to reduce the force of nearly 90,000 to about 68,000 by the end of September, with most of the remaining combat troops due to be pulled out by the end of 2014.