Siney asked the miners to join the union, and thousands did so that day. Some miners faced additional burdens of prejudice and persecution. In the 1840s, 1850s, and 1860s, some 20,000 Irish workers had arrived in Schuylkill County. It was a time of rampant beatings and murders in the mining district.

British and Irish newspapers reported about the Mollies in Ireland in the nineteenth century. Thomas Campbell Foster in The Times on 25 August 1845 traced the commencement of "Molly Maguireism" to Lord Lorton ejecting tenants in Ballinamuck, County Longford, in 1835. An "Address of 'Molly Maguire' to her children" containing twelve rules was published in Freeman's Journal on 7 July 1845. The person making the address claimed to be "Molly Maguire" of "Maguire's Grove, Parish of Cloone", in County Leitrim. The rules advised Mollies about how they should conduct themselves in land disputes and were an attempt to direct the movement's activities:

The Molly Maguires were also active in Liverpool, England, where many Irish people settled in the 19th century, and many more passed through Liverpool on their way to the United States or Canada. The Mollies are first mentioned in Liverpool in an article in The Liverpool Mercury newspaper on 10 May 1853. The newspaper reported that, "a regular faction fight took place in Marybone amongst the Irish residents in that district. About 200 men and women assembled, who were divided into four parties – the 'Molly Maguires', the 'Kellys', the 'Fitzpatricks' and the 'Murphys' – the greater number of whom were armed with sticks and stones. The three latter sections were opposed to the 'Molly Maguires' and the belligerents were engaged in hot conflict for about half an hour, when the guardians of the peace interfered."

Franklin B. Gowen, the President of the Philadelphia and Reading Railroad, and of the Philadelphia and Reading Coal and Iron Company and "the wealthiest anthracite coal mine owner in the world", hired Allan Pinkerton's services to deal with the Mollies. Pinkerton selected James McParland (sometimes called McParlan), a native of County Armagh, to go undercover against the Mollies. Using the alias "James McKenna", he made Shenandoah his headquarters and claimed to have become a trusted member of the organization. His assignment was to collect evidence of murder plots and intrigue, passing this information along to his Pinkerton manager. He also began working secretly with a Pinkerton agent assigned to the Coal and Iron Police for the purpose of coordinating the eventual arrest and prosecution of members of the Molly Maguires. Although there had been fifty "inexplicable murders" between 1863 and 1867 in Schuylkill County, progress in the investigations was slow. There was "a lull in the entire area, broken only by minor shootings". McParland wrote: I am sick and tired of this thing. I seem to make no progress.

Wages were low, working conditions were atrocious, and deaths and serious injuries numbered in the hundreds each year. On 6 September 1869, a fire at the Avondale Mine in Luzerne County, took the lives of 110 coal miners. The families blamed the coal company for failing to Finance a secondary exit for the mine.

While Kenny observes that the AOH was "a peaceful fraternal society", he does note that in the 1870s the Pinkerton Agency identified a correlation between the areas of AOH membership in Pennsylvania, and the corresponding areas in Ireland from which those particular Irish immigrants emigrated. The violence-prone areas of Ireland corresponded to areas of violence in the Pennsylvania coalfields. In his book Big Trouble, which traces McParland's history, Writer J. Anthony Lukas has written: "The WBA was run by Lancashire men adamantly opposed to violence. But [Gowen] saw an opportunity to paint the union with the Molly brush, which he did in testimony before a state investigating committee ... 'I do not charge this Workingmen's Benevolent Association with it, but I say there is an association which votes in secret, at night, that men's lives shall be taken ... I do not blame this association, but I blame another association for doing it; and it happens that the only men who are shot are the men who dare disobey the mandates of the Workingmen's Benevolent Association.'"

1873-79 (see Panic of 1873) were marked by one of the worst depressions in the nation's history, caused by economic overexpansion, a stock market crash, and a decrease in the money supply. By 1877 an estimated one-fifth of the nation's workingmen were completely unemployed, two-fifths worked no more than six or seven months a year, and only one-fifth had full-time jobs. Labor organizers angrily watched railway Directors riding about the country in luxurious private cars while proclaiming their inability to pay living wages to hungry working men.

A Pinkerton agent, Robert J. Linden, was brought in to support McParland while serving with the Coal and Iron Police. On August 29, 1875, Allan Pinkerton wrote a letter to George Bangs, Pinkerton's general superintendent, recommending vigilante actions against the Molly Maguires: "The M.M.'s are a species of Thugs... Let Linden get up a vigilance committee. It will not do to get many men, but let him get those who are prepared to take fearful revenge on the M.M.'s. I think it would open the eyes of all the people and then the M.M.'s would meet with their just deserts." On 10 December 1875, three men and two women were attacked in their home by masked men. Author Anthony Lukas wrote that the attack seemed "to reflect the strategy outlined in Pinkerton's memo".

The first trial of defendants McGeehan, Carroll, Duffy, James Boyle, and James Roarity for the killing of Yost commenced in May 1876. Yost had not recognized the men who attacked him. Although Kerrigan has since been described, along with Duffy, as hating the night watchman enough to plot his murder, Kerrigan became a state's witness and testified against the union Leaders and other miners. However, Kerrigan's wife testified in the courtroom that her husband had committed the murder. She testified that she refused to provide her husband with clothing while he was in prison, because he had "picked innocent men to suffer for his crime". She stated that she was speaking out voluntarily, and was only interested in telling the truth about the murder. Gowen cross-examined her, but could not shake her testimony. Others supported her testimony amid speculation that Kerrigan was receiving special treatment due to the fact that McParland was engaged to his sister-in-law, Mary Ann Higgins. This trial was declared a mistrial due to the death of one of the jurors. A new trial was granted two months later. During that trial Fanny Kerrigan did not testify. The five defendants were sentenced to death. Kerrigan was allowed to go free.

On June 21, 1877, six men were hanged in the prison at Pottsville, and four at Mauch Chunk, Carbon County. A scaffold had been erected in the Carbon County Jail. State militia with fixed bayonets surrounded the prisons and the scaffolds. Miners arrived with their wives and children from the surrounding areas, walking through the night to honor the accused, and by nine o'clock "the crowd in Pottsville stretched as far as one could see." The families were silent, which was "the people's way of paying tribute" to those about to die. Thomas Munley's aged father had walked more than 10 mi (16 km) from Gilberton to assure his son that he believed in his innocence. Munley's wife arrived a few minutes after they closed the gate, and they refused to open it even for close relatives to say their final good-byes. She screamed at the gate with grief, throwing herself against it until she collapsed, but she was not allowed to pass. Four (Alexander Campbell, John "Yellow Jack" Donahue, Michael J. Doyle and Edward J. Kelly) were hanged on June 21, 1877, at a Carbon County prison in Mauch Chunk (renamed Jim Thorpe in 1953), for the murders of John P. Jones and Morgan Powell, both mine bosses, following a trial later described by a Carbon County judge, John P. Lavelle, as follows:

Campbell, just before his execution, allegedly slapped a muddy handprint on his cell wall stating "There is proof of my words. That mark of mine will never be wiped out. It will remain forever to shame the county for hanging an innocent man." Doyle and Hugh McGeehan were led to the scaffold. They were followed by Thomas Munley, James Carroll, James Roarity, James Boyle, Thomas Duffy, Kelly, Campbell, and "Yellow Jack" Donahue. Judge Dreher presided over the trials. Ten more condemned, Thomas Fisher, John "Black Jack" Kehoe, Patrick Hester, Peter McHugh, Patrick Tully, Peter McManus, Dennis Donnelly, Martin Bergan, James McDonnell and Charles Sharpe, were hanged at Mauch Chunk, Pottsville, Bloomsburg and Sunbury over the next two years. Peter McManus was the last Molly Maguire to be tried and convicted for murder at the Northumberland County Courthouse in 1878.

In November, McAllister was convicted. McParland's testimony in the Molly Maguires trials helped send ten men to the gallows. The defense attorneys repeatedly sought to portray McParland as an agent provocateur who was responsible for not warning people of their imminent deaths. For his part, McParlan testified that the AOH and the Mollies were one and the same, and the defendants guilty of the murders. In 1905, during the Colorado Labor Wars, in preparation for a trial, McParlan told another witness, Harry Orchard, that "Kelly the Bum" not only had won his freedom for testifying against union Leaders, he had been given $1,000 to "subsidize a new life abroad". McParlan had been attempting to convince Orchard to accuse Bill Haywood, leader of the Western Federation of Miners (WFM), of conspiracy to commit another murder. Unlike the Mollies, the WFM's union leadership was acquitted. Orchard alone was convicted, and spent the rest of his life in prison.

Many accounts of the Molly Maguires that were written during, or shortly after, the period offer no admission that there was widespread violence in the area, that vigilantism existed, nor that violence was carried out against the miners. In 1910, industrialist and Historian James Ford Rhodes published a major scholarly analysis in the leading professional history journal:

A legal self-help organization for Irish immigrants existed in the form of the Ancient Order of Hibernians (AOH), but it is generally accepted that the Mollies existed as a secret organization in Pennsylvania, and used the AOH as a front. However, Joseph Rayback's 1966 volume, A History of American Labor, claims the "identity of the Molly Maguires has never been proved". Rayback writes:

In 1979, Pennsylvania Governor Milton Shapp granted a posthumous pardon to John "Black Jack" Kehoe after an investigation by the Pennsylvania Board of Pardons. The request for a pardon was made by one of Kehoe's descendants. John Kehoe had proclaimed his innocence until his death. The Board recommended the pardon after investigating Kehoe's trial and the circumstances surrounding it. Shapp praised Kehoe, saying the men called "Molly Maguires" were "martyrs to labor" and heroes in the struggle to establish a union and fair treatment for workers. And "... [I]t is impossible for us to imagine the plight of the 19th Century miners in Pennsylvania's anthracite region" and that it was Kehoe's popularity among the miners that led Gowen "'to fear, despise and ultimately destroy [him]'".

After six months the strike was defeated and the miners returned to work, accepting the 20 percent cut in pay. But miners belonging to the Ancient Order of Hibernians continued the fight. McParland acknowledged increasing support for the Mollies in his reports: Men, who last winter would not notice a Molly Maguire, are now glad to take them by the hand and make much of them. If the bosses exercise tyranny over the men they appear to look to the association for help. Lukas observes that the defeat was humiliating, and traces the roots of violence by the Mollies in the aftermath of the failed strike: Judges, lawyers, and policemen were overwhelmingly Welsh, German, or English ... When the coalfield Irish sought to remedy their grievances through the courts, they often met delays, obfuscation, or doors slammed in their faces. No longer looking to these institutions for justice, they turned instead to the Mollies.... Before the summer was over, six men—all Welsh or German—paid with their lives.

Later Liverpool newspaper articles from the same time period refer to assaults by Mollies against other Irish Liverpudlians. The "Molly Maguire club" or "Molly's Club" was described as a "mutual defence association" that had been "formed for the mutual assistance of the members when they got into ‘trouble’, each member subscribing to the funds". Patrick Flynn was the secretary of the Liverpool Molly Maguire Clubs in the 1850s and their headquarters was in an alehouse in Alexander Pope Street also known as Sawney Pope Street. The Liverpool branch of the Molly Maguires was known for its gangsterism rather than any genuine concern for the welfare of Irish people.

Some historians (such as Philip Rosen, former curator of the Holocaust Awareness Museum of the Delaware Valley) believe that Irish immigrants brought a form of the Molly Maguires organization into America in the 19th century, and continued its activities as a clandestine society. They were located in a section of the anthracite coal fields dubbed the Coal Region, which included the Pennsylvania counties of Lackawanna, Luzerne, Columbia, Schuylkill, Carbon, and Northumberland. Irish miners in this organization employed the tactics of intimidation and violence used against Irish landlords during the "Land Wars" yet again in violent confrontations against the anthracite, or hard coal, mining companies in the 19th century.