In the latest dramatic twist in the high-profile case, a court in Florence on Thursday sentenced Knox to 28 years and six months in prison for killing Meredith Kercher in the university town of Perugia.
Knox was following the proceedings from her hometown of Seattle in the United States, where she has lived since a previous acquittal in 2011, which Italian prosecutors appealed.
Her lawyers now plan to appeal this latest conviction in turn to the Italian Supreme Court, but if they fail Knox could find herself flying back to a country where she has already spent four years in jail.
"As popular as she is here and as pretty as she is here - because that's what this is all about, if she was not an attractive woman we wouldn't have the group love-in -- she will be extradited if it's upheld," said Harvard law professor Alan Dershowitz.
While Knox has won a great deal of support in the United States where she is seen as the innocent victim of a miscarriage of justice, Dershowitz said there are no legal grounds for preventing extradition.
Nor would it play well diplomatically, given that the United States demands more extraditions than any other nation, he said.
"The Italian legal system, though I don't love it, is a legitimate legal system and we have a treaty with Italy so I don't see how we would resist," he told AFP.
"We're trying to get Snowden back -- how does it look if we want Snowden back and we won't return someone for murder?" he asked, referring to fugitive intelligence contractor Edward Snowden.
Knox's supporters argue she should be protected from extradition because the Italian system - which allows prosecutors to appeal a verdict -- violates the US legal prohibition on double jeopardy: trying someone twice for the same crime.
Legal experts attach little weight to this argument.
"They always forget she was convicted first," said Julian Ku, who teaches transnational law at Hofstra University.
Knox and her former Italian boyfriend Raffaele Sollecito served four years in prison for the murder before being released after an appeal led to their 2011 acquittal.
The Italian Supreme Court overturned that ruling in 2013, sending the case back for re-trial.
Italy must first file an extradition request with the US State Department, which will then determine if it should ask the Justice Department to detain Knox.
Knox then has the right to challenge her extradition in a US court.
"The chances of her winning that are not high because there has to be some very strong claim she'd have to make to block her extradition," Ku said in a telephone interview.
While the "public notoriety" of the case could theoretically push the State Department to deny the request, Ku said it would be difficult to argue that the Italians didn't meet US standards of justice.
"I followed the trial, it was slow but I never got the sense that it was unfair," he said.
A US State Department official confirmed that there is an extradition treaty between the United States and Italy, but declined to comment on Thursday's verdict and trial.