Clinton addressed State Department employees in the afternoon before leaving her post.
"As I look back over these past four years, I am very proud of the work we have done together. Of course, we live in very complex and even dangerous times, as we saw again just today at our embassy in Ankara, where we were attacked and lost one of our foreign service nationals and others injured," Clinton said. "But I spoke with the ambassador, and the team there, I spoke with my Turkish counterpart and I told them how much we valued their commitment and their sacrifice.
Clinton said she sees hope for the future.
"I know that the world we are trying to help bring into being in the 21st century will have many difficult days, but I am more optimistic today than I was when I stood here four years ago, because I have seen day after day the many contributions that our diplomats and development experts are making to help ensure that this century provides the kind of peace, progress and prosperity that not just the United States, but the entire world, especially young people, so richly deserve."
Kerry, who resigned his Senate seat after his confirmation earlier this week, was sworn in Friday during a private ceremony. Kerry officially begins his duties Monday.
During his confirmation hearing, Kerry told his colleagues he believed Clinton set the bar high for "tireless efforts."
Clinton has said she is looking forward to the next chapter in her life. Although she has denied it, there is widespread speculation she will be a presidential candidate in 2016 and a super PAC supporting Clinton has been established.
Clinton outlined her vision of diplomacy Thursday during a speech at the Council on Foreign Relations in Washington, reiterating economic development and use of social media were key complements to military force and other, more traditional instruments of power, The New York Times reported.
"We face challenges, from financial contagion to climate change to human and wildlife trafficking that spill across borders and defy unilateral solutions," she said. "The geometry of global power has become more distributed and diffused as the challenges we face have become more complex and crosscutting."
The immediate problems Kerry will face include the deteriorating situation in Syria, turmoil in Egypt, the emergence of affiliates of al-Qaida in North Africa and the standoff with Iran over its nuclear program, she said.
"I don't think the window can remain open for too much longer," Clinton said of Iran. "I am not going to put days, weeks or months on it."
Reflecting on her tenure, Clinton said she did everything she could to tamp down the Syrian conflict by working to organize the opposition, backing humanitarian assistance and working to isolate President Bashar Assad.
"I've done what was possible to do," Clinton said. "The worst kind of predictions about what could happen internally, and spilling over the borders of Syria, are certainly within the realm of the possible now."
Notable deaths of 2014 [PHOTOS]