"I am tremendously relieved and grateful for the decision of the Supreme Court of Italy," Knox said in a statement shortly after Italy's Court of Cassation cleared her and Italian ex-boyfriend Raffaele Sollecito.
Knox, convicted with Sollecito for a second time last year for taking part in the brutal knife slaying of Kercher, has always vehemently maintained her innocence.
"The knowledge of my innocence has given me strength in the darkest times of this ordeal," Knox said.
"And throughout this ordeal, I have received invaluable support from family, friends and strangers. To them, I say: Thank you from the bottom of my heart.
"Your kindness has sustained me. I only wish that I could thank each and every one of you in person."
A separate statement from Knox's family expressed "profound gratitude" to those who had championed the former student's innocence.
"Countless people – from world-renowned DNA experts, to former FBI agents, to everyday citizens committed to justice – have spoken about her innocence," it said.
"We are thrilled with and grateful for today's decision from the Supreme Court of Italy. And we are grateful beyond measure for all that so many of you have done for her."