The Jury Room re-examines real murder cases in which convicted killers have always maintained their innocence. The accepted facts of each case are presented, as originally seen by the actual trial judge and jury, to twelve members of a specially selected jury. Ex-Detective Chief Inspector Colin Sutton represents the prosecution and barrister Matt Stanbury speaks for the defence, while renowned crime reporter Will Hanrahan helps the jury and the viewers to connect the dots.

Each sitting offers either revelatory new evidence, or a more advanced analysis of pre-existing evidence, that may influence the jury's judgment. The action unfolds in real time as the women and men in the jury room consider each defendant's fate.