On Thursday night, Knox posted a lengthy, impassioned thread of tweets prompted by press for newly released film Stillwater. The motion picture, staring Damon and directed by McCarthy, is "loosely inspired" by the trials of Knox.
In 2007, Knox was convicted with her Italian boyfriend at the time, Raffaele Sollecito, and Ivorian-born Rudy Guede, of killing her British roommate Meredith Kercher in Perugia, Italy.
After a series of legal flip-flops, Knox and Sollecito were acquitted.
In her thread, Knox argued that despite being cleared, media products like Stillwater continue to use her, and not Guede, as a focal character in their coverage of the murder.
“Does my name belong to me? My face? What about my life? My story? Why does my name refer to events I had no hand in?," she began.
"I return to these questions because others continue to profit off my name, face, & story without my consent. Most recently, the film #STILLWATER.”
Stillwater stars Damon as a construction worker who flies to France after his daughter Allison - played by Abigail Breslin - is jailed for murdering her lover. Allison also asks the killer to "get rid" of the victim's body.
Ms Knox complained: "How do you think that impacts my reputation?
"I continue to be accused of 'knowing something I’m not revealing,' of 'having been involved somehow, even if I didn’t plunge the knife.'
"So Tom McCarthy’s fictionalised version of me is just the tabloid conspiracy guilter version of me."
"But that didn’t inspire him to ask me how it felt to be in my shoes," she wrote.
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She also predicted that Damon and McCarthy will "profit handsomely" from "telling a story that distorts [her] reputation in negative ways".
The pair weren't the only ones called out by Ms Knox, she also hit out at various media platforms for their coverage, including FOX, The New York Times, The New York Post and Deadline.
"15 years later, my name is the name associated with this tragic series of events, of which I had zero impact on. Meredith’s name is often left out, as is Rudy Guede’s," she said.
At the Cannes Film Festival earlier this month, where “Stillwater” was screened, McCarthy said Knox’s case served as an “initial inspiration point but not much beyond that. I just had a daughter then and I thought how it would be like.”
In a later interview with The Associated Press to promote “Stillwater,” McCarthy said he “didn’t want to kind of copy or mimic” Knox’s legal ordeal.
“It’s loosely inspired by that case, so I didn’t want to try and do a recreation of that. I want Allison to kind of be her own stand-alone character, but it was definitely great to have that for a reference.”
The studio releasing the film, Focus Features, didn’t immediately respond to emails sent by The Associated Press on Friday.