Musolino was born on September 24, 1876, in Santo Stefano in Aspromonte, a rugged area in the Calabria region of southern Italy.

[2][4] On September 28, 1898, at a trial before the Corte d'Assise of Reggio Calabria, Musolino was sentenced to 22 years of hard labor for attempted murder;[4][5][6] experts noted that his conviction was largely based on circumstantial evidence.

[8] Seeking to exact revenge on those who had testified against him (most of whom he felt had done so in bad faith) Musolino escaped from his prison in Gerace on January 19, 1899.

[3] As news spread of his story, escape, and string of murders, Musolino was hailed as a hero by Calabrians and others in southern Italy.

[8] He garnered significant support and sympathy from the citizens of a region where seeking revenge, often in a violent manner, was typically seen as the best way to bring about social justice, given that they felt Musolino had been wronged.

[6][8] During interrogation sessions over the following days, Musolino continued to lie about his identity, insisting that his name was Francesco Colafiore and providing a fictionalized life story.

[6] However, due to the overwhelming public support for Musolino and his cause in southern Italy, the courts were forced to move him and hold a trial in Lucca, Tuscany; this was determined to be the only way to ensure an impartial jury.

[11] Examples cited included his refusal to participate in the trial as long as he was being forced to wear standard convict (which he already was, as a prison escapee) attire; instead, he demanded the right to dress formally.

Additionally, he interrupted witnesses and the judge on several occasions as they were speaking, often to applause as well as tears from Calabrians present at the trial who were moved by Musolino's story.

[12] Musolino also did not directly answer any questions asked of him when they were posed during the trial; instead, he would respond by retelling very long stories of his crimes and early life that were perceived by observers to have been out-of-context, again eliciting a great emotional response.

A number of criminologists and psychiatrists were called upon to examine Musolino and determine if he was of sound enough mind;[8] besides his peculiar behavior, it was noted that he had a family history of epilepsy and alcoholism, and numerous relatives were deemed by doctors to be apoplectic.

[13] Lombroso wrote that the family histories of epilepsy and criminality were intertwined and greatly contributed to Musolino's epileptic attacks and the resulting violent acts he committed.

[1][13] While he was being held in Catanzaro prior to this trial, Musolino had several episodes of epileptic seizures, although the prison director said he believed he was faking it.

[20] Cicciu Busacca also dedicated an entire album to Musolino, named La storia di lu briganti Musulinu.