"I do not believe in the false choice between fiscal discipline and a strong national defence," he wrote in a letter to the Pentagon.
Mr Panetta, sworn in on Friday, promised to be a strong advocate for the troops and their families.
He takes over as the US begins to withdraw troops from Afghanistan.
In June US President Barack Obama announced that 10,000 US troops would leave Afghanistan this year, with an additional 23,000 withdrawn during 2012.
In his letter, Mr Panetta reminded Pentagon staff and military personnel that "our nation is at war", and promised "we will persist in our efforts to disrupt, dismantle, and ultimately defeat al-Qaeda".
Mr Panetta will also be tasked with implementing the end to the ban on gays and lesbians serving openly in the US military.
Since 2009 he has been CIA director; he now replaces Robert Gates, who was appointed by President George W Bush in 2006 and whom Mr Obama kept on in the role.
Mr Panetta's redeployment to the Pentagon comes as part of a reshuffling of Mr Obama's national security staff. Gen David Petraeus, the former commander of Nato forces in Afghanistan, takes over from him at the CIA.
Among his many challenges, Mr Panetta may have to manage cuts to the Pentagon budget, as the US government is currently running a $1.5 trillion (£934.8bn) budget deficit.
The Pentagon's 2011 budget is $530bn, and Mr Obama in April called for $400bn in defence spending cuts over the next 12 years.
"We must preserve the excellence and superiority of our military while looking for ways to identify savings," Mr Panetta wrote.
"While tough budget choices will need to be made, I do not believe in the false choice between fiscal discipline and a strong national defence. We will all work together to achieve both."
Mr Panetta, 73, a Democrat, represented a constituency in California in the US House of Representatives from 1977 to 1993. He was a senior budget aide, then White House chief of staff under President Bill Clinton until 1996.
He also served as an intelligence officer in the US Army in the 1960s.