The convictions of Amanda Knox and Raffaele Sollecito for the murder of UK student Meredith Kercher have been quashed by Italy's top appeals court.
It is the final ruling in the case, following three previous court decisions over the 2007 murder.
Ms Kercher, 21, was stabbed to death in a Perugia flat she shared with Ms Knox.
American Ms Knox, 27, said she was "full of joy" after being acquitted, but the mother of Ms Kercher, who was from London, said she was "shocked".
Ms Knox and Mr Sollecito, her Italian ex-boyfriend, were initially found guilty of the murder in 2009.
They were freed in 2011 after the convictions were overturned, but they were reinstated by another court last year.
Despite being cleared of the murder charge, the guilty verdict against Ms Knox for the slander of Patrick Lumumba - a bar owner she falsely accused of the crime - has been upheld.
The presiding judge confirmed a three-year sentence would remain. That time has been served.
Ms Knox had spent four years in prison during the trial, and could seek compensation for the extra year served, BBC Europe correspondent Gavin Lee said.
'Full of joy'
Ms Knox and Mr Sollecito had always maintained their innocence and the decision by the Court of Cassation puts an end to their long legal battle.
The reasoning behind the decision will be made public in 90 days.
"I'm still absorbing the present moment," Ms Knox said, speaking outside her mother's house in Seattle.
She expressed thanks "for the justice I've received and for the support I've had from everyone".
"Meredith was my friend," she added, "she deserved so much in this life."
Gavin Lee, BBC Europe correspondent in Rome
It has been a seven-year trial, and late on Friday night, after nine hours of discussion, five appeal court judges in Rome's supreme court stepped out to deliver a definitive acquittal of Amanda Knox and Raffaele Sollecito, over the murder of Meredith Kercher.
No reason was given. A brief statement was read by the presiding judge - justification will be delivered, in writing, within 90 days, in accordance with Italian law.
Neither defendant was in court, but there were cheers from both defence teams, who spoke of their surprise - an acquittal being a rarity in Italian supreme court hearings.
Lawyer Carlo Della Vedova broke the news to Ms Knox by phone, who cried with happiness, saying she now wants to "recover from this nightmare".
The Kercher family have not been in court for this hearing, but prosecution lawyer Francesco Maresca spoke of their concern that they won't ever learn the truth about what happened to Ms Kercher eight years ago.
Prof Greg Hampikian, a friend of the Knox family who also worked on the DNA evidence for Ms Knox's defence, told BBC Radio 5 live that "everybody is very happy to see this finished, so they can get on with their lives".
"She's trying to start her life as a young woman, so hopefully this will be a really wonderful change and a new day for them and for Raffaele and his folks," he said.
"I hope the Kerchers can find peace as well. It's just been an up and down thing for everyone for so long."
The lawyer for Ms Kercher's family, Francesco Maresca, expressed his disappointment, saying: "I think that it's a defeat for the Italian justice system."
Arline Kercher, Meredith's mother, said she was "very shocked" by the court's decision.
"They have been convicted twice so it's a bit odd that it should change now," she said.
Ms Kercher, from Coulsdon in south London, was on a one-year student exchange in Perugia when her throat was cut in the flat she shared with Ms Knox.
Prosecutors claimed she was killed as part of a sex game that went wrong.
The Leeds University student's body was found under a duvet in her bedroom, which had been locked from the inside.
Days after the killing, Ms Knox and her then-boyfriend, Mr Sollecito, 31, were arrested.
They were convicted of murder in 2009 by a court in Perugia.
But in 2011, a jury cleared both defendants of the charge, after doubts were raised over the handling of DNA evidence.
A retrial was ordered after prosecutors argued that important evidence had been disregarded. In 2014, the guilty verdicts were reinstated.
Another man, Rudy Hermann Guede, born in Ivory Coast, was convicted of murder in a separate trial and is serving a 16-year sentence.
The court's ruling against Guede stated that he did not act alone, and the 2014 verdicts against Ms Knox and Mr Sollecito said they wielded knives, Guede held the victim down and committed a sexual assault and Ms Knox "delivered the only mortal blow".
That 2014 ruling has now been overturned, so no-one now stands convicted of acting with Guede to kill Ms Kercher.
Knox family reaction
David Willis, BBC News, Seattle
Whoops of joy erupted from the Knox family home in the sleepy Seattle neighbourhood of Arbor Heights as the verdict was announced.
All morning family and friends had been coming and going - members of the "Friends of Amanda" campaign that has lobbied so tirelessly on her behalf.
They and many others in America's Pacific North West have long been convinced Amanda Knox is the victim of a major miscarriage of justice.
One supporter, former Judge Michael Heavey, told the BBC it had been a "modern-day witch hunt".
Amanda Knox is now free to travel outside the US, and, at the age of 27, to plan for her future - a future free of the risk of being extradited to Italy to serve out the remainder of a 28-and-a-half year sentence.