"There's no question, as you confront [Islamic extremists] in Yemen, in Somalia, in Libya, that they're going to ultimately try to relocate. So, you know that certainly, I think, is a consequence," Panetta said Monday.
His comments come a day after the French military launched a massive campaign to oust extremist groups allied with al Qaeda's West African cell, known as al Qaeda in the Islamic Magreb (AQIM), out of northern Mali.
A loose coalition of AQIM fighters and Malian separatists closed off the northern part of the country last March, in the wake of a successful military coup in the country.
French warplanes have been executing airstrikes against AQIM targets in the north to devastating effect since Sunday, while al Qaeda gunmen have begun carrying out raids against towns and villages in southern Mali in response to the aerial offensive.
On Monday, Panetta told reporters Washington had a "responsibility" to provide military and intelligence support to French troops for the duration of their operations in Mali.
However, the Defense chief noted the emergence of Mali as a al Qaeda stronghold was due in no small part to American counterterrorism efforts in the region.
"I think it's understandable that, as we've confronted them in each of these other areas, that they were going to try to move and establish a base of operations wherever they could," the Pentagon chief said.
"I think that was probably going to happen under any circumstances, but the fact is that we've been watching it for a long time, we have been paying attention to it, we haven't ignored the fact that they have made efforts to locate there," Panetta added.
American military and intelligence leaders began stepping up their attacks via unmanned drone strikes against al Qaeda affiliates in Yemen back in 2009, when the group's cell, known as al Qaeda in the Arabian Peninsula, attempted to blow up a U.S. commerical airliner.
Most recently, U.S. forces ramped up drone attacks in Libya in the aftermath of last March's deadly raid on the U.S. Consulate in Benghazi, Libya, which ended in the deaths of four Americans, including U.S. Ambassador Chris Stevens.
On Sunday, the White House informed Congress that American surveillance and air assets were used in a failed attempt by French special forces to rescue a French intelligence agent who had been held hostage by Islamic extremists in Somalia.
The intelligence operative and two French special forces operators were killed during the botched raid.
The ongoing counterterrorism effort in Mali and elsewhere on the continent only underscores the legitimate threat posed by AQIM and other al Qaeda affiliates in the region to the U.S. and its allies, according to Panetta.
"We're concerned ... any time Al Qaida establishes a base of operations," Panetta said.
Even though American intelligence has not picked up any recent information on AQIM plots against the United States or Europe, "that ultimately that still remains their [main] objective," according to Panetta.
"It's for that reason that we have to take steps now to ensure that AQIM does not get that kind of traction," the DOD chief added.