Dassey was convicted in 2007 of the murder of photographer Teresa Halbach. In overturning the conviction, the judge cited the manner in which a confession was obtained from Dassey, who according to court documents has a low IQ.
Prosecutors have 90 days to bring Dassey, now 26, to trial again or he will be released.
His uncle, Steven Avery, the subject of "Making a Murderer," is in a Wisconsin prison also serving time for Halbach's murder.
Two attorneys who have represented Dassey through his appeals process released a statement saying they are "overwhelmed."
"The court's decision rests on a fundamental principle that is too often forgotten by courts and law enforcement officers: Interrogation tactics which may not be coercive when used on adults are coercive when used on juveniles, particularly young people like Brendan with disabilities," attorneys Steven A. Drizin and Laura Nirider said.
The statement added that the legal team will take the appropriate next steps toward getting Dassey released as soon as possible, but didn't specify the next legal move.
The 10-part Netflix series, released last December, renewed interest in Avery's ongoing legal troubles, leading to calls for his release and a petition seeking a presidential pardon
Many of the elements of the case bothered observers.
For example, Dassey -- described in the judge's ruling as having an IQ "assessed as being in the low average to borderline range" -- was questioned without his mother present and appeared to be eager to tell sheriff's officers what they wanted to hear.
Some viewers said that after watching the documentary they believed that the sheriff's office planted evidence to frame Avery for the crime.
Avery's two convictions
Avery was convicted in 1985 in the rape of jogger Penny Beerntsen on a beach near her home in Manitowoc, Wisconsin. After serving 18 years in prison he was exonerated based on DNA evidence connecting the attack to another man.
Avery was released in 2003 and filed a lawsuit against Manitowoc County for wrongful conviction and imprisonment. Two years later, while the suit was still pending, he was arrested in the death of Halbach, whose charred remains were found on his family's auto salvage yard.
Prosecutors laid out their case: Halbach's Toyota RAV4 (which contained blood, including Avery's) was found on the Avery family's lot. Tissue and bone fragments that matched Halbach's DNA profile were found outside Avery's mobile home.
Dassey, then 16, confessed to authorities that he assisted his uncle in raping and killing Halbach. He later recanted.
Federal judge William E. Duffin overturned Dassey's convictions based on the way the confession was attained, calling it "so clearly involuntary in a constitutional sense that the court of appeals' decision to the contrary was an unreasonable application of clearly established federal law."
The judge said he didn't believe investigators tried to trick Dassey into confessing but instead misunderstood the constitutional ramifications of telling him that they already knew everything that happened and he would be OK if he told the truth.
"Dassey's confession was, as a practical matter, the entirety of the case against him," the judge wrote.
Duffin also criticized Dassey's first attorney, Leonard Kachinsky, who the judge wrote, was excited to be on the case because of all the media attention. In May 2006, state investigators interviewed Dassey but Kachinsky didn't attend.
Duffin wrote that Kachinsky's conduct throughout the case was tactically and ethically inexcusable. However, it was not a conflict of interest.
"I was surprised by it, because when a motion to suppress is appealed, usually the findings of the trial judge, in this case Judge Fox, is usually upheld unless it's fairly erroneous," Kachinsky told CNN affiliate WLUK
in a phone interview.
New series in the works
CNN reached out to former Calumet County District Attorney Ken Kratz, who prosecuted both cases, but didn't receive an immediate response.
Kratz has criticized filmmakers Laura Ricciardi and Moira Demos, saying they left out crucial evidence that pointed to Avery's guilt -- an accusation the pair has denied.
Netflix said last month it has started production on new episodes of its docuseries that will act as a follow-up to Season 1.
The new season, the company said, will revisit the case and be "an in-depth look at the high-stakes post-conviction process" and explore the "emotional toll" on all involved.