While on death row, Panzram was befriended by a guard named Henry Lesser (1902–1983) who would give him money to buy cigarettes. Panzram was so astonished by this one act of kindness that after Lesser provided him with writing materials Panzram, while waiting his execution, wrote a detailed summary of his crimes and nihilistic philosophy. In this he made it quite clear that he did not repent in the least of all the robberies, murders, rapes, and arsons he had been involved in. It began with a straightforward statement:

Born in East Grand Forks, Minnesota, the son of East Prussian immigrants Johann "John" and Matilda Panzram, Carl was raised on his family's farm with five siblings. Carl Panzram felt odd from a young age: by the age of five or six he was a liar and thief and claimed to become meaner the older he grew. In 1899 Panzram was in Juvenile Court on a charge of being drunk and disorderly; in 1903 Panzram was in County Jail for being drunk and incorrigible; In 1903, at the age of 11, he stole some cake, apples, and a revolver from a neighbor's home. Soon after, his parents sent him to the Minnesota State Training School October 11, 1903. While there, he was repeatedly beaten, tortured, and raped by staff members in what attendees dubbed "The Painting House", because children would leave "painted" with bruises and blood. Panzram hated this place of torture so much that he decided to burn it down, and did so without detection July 7, 1905 In January 1906, Panzram was reported to be paroled from Red Wing Training School after stealing money from his mothers pocketbook. By his teens, he was an alcoholic and was repeatedly in trouble with the authorities, often for burglary and theft. He ran away from home at the age of 14 in January 1906 to become a hobo on the rails . He often traveled via train cars; he later claimed that on one train he was gang raped by a group of hobos.

In 1907, at the age of 15, after getting drunk in a saloon in Montana, Panzram enlisted in the U.S. Army. Shortly thereafter he was convicted of larceny and served a prison sentence from 1908 to 1910 at Fort Leavenworth's United States Disciplinary Barracks. Then-Secretary of War william Howard Taft approved the sentence. Panzram later claimed that any goodness left in him was smashed out during his Leavenworth imprisonment.

Winter, 1910 Panzram alleged in his 1929 autobiography that after serving a short sentence at Rusk Texas, he claimed to have gone to Juarez, Mexico to try to enlist in the Federal Mexican Army; he then left on a train for Del Rio, Texas and got off in a small town 50 to 100 miles east of El Paso, Texas where about a mile south of that town he alleged to have abducted, assaulted, kicked and strangled a man and then stole $35.00 from the victim.

Summer 1911 Panzram aka "Jefferson Davis" arrested Fresno California for stealing a bicycle; sentenced to 6 months in county jail. Escaped after 30 days

April 27, 1913 Panzram aka "Jefferson Davis" admitted to State Prison, Deer Lodge Montana; escapes November 13, 1913. Within a week arrested as "Jeff Rhoades" in Three Forks, Montana for burglary and returned to Deer Lodge for an additional year.

On June 1, 1915, Panzram burglarized a house in Astoria, Oregon, but was arrested soon after while attempting to sell some of the stolen items. He was sentenced to seven years in prison, to be served at the Oregon State Penitentiary in Salem, where he arrived on June 24. Warden Harry Minto believed in harsh treatment of inmates, including beatings and isolation, among other disciplinary measures. Later, Panzram stated that he swore he "would never do that seven years and I defied the warden and all his officers to make me." Later that year, Panzram helped fellow inmate Otto Hooker escape from the prison. While attempting to evade recapture, Hooker killed Minto, marking Panzram's first known involvement in a murder, as an accessory before the fact.

Panzram was disciplined several times while at Salem, including 61 days in solitary confinement, before escaping on September 18, 1917. After two shootouts, he was recaptured and returned to the prison. On May 12, 1918, he escaped once again by sawing through the bars of his cell, and caught a freight train heading east. He began going by the name John O’Leary and shaved off his moustache. He would never return to the North West.

October 26, 1920 Panzram aka "John O' Leary" arrested Stamford CT for burglary and possession of a loaded handgun;

Panzram then caught a ship to Africa and landed in Luanda, Portuguese Angola. In 1921 Panzram is foreman of an Oil rig in Angola, Africa [he later burned the rig down out of sheer meaness]. He later claimed that while there, he raped and killed an 11- or 12-year-old boy. In his confession to this murder, he wrote: "His brains were coming out of his ears when I left him and he will never be any deader." He also claimed that he hired a boat with six rowers, shot the rowers with a German Luger pistol, and threw their bodies to the crocodiles.

After returning to the U.S., Panzram asserted that he raped and killed two small boys, beating one to death with a rock on July 18, 1922, in Salem, Massachusetts and strangling the other later that year near New Haven. Panzram claimed that, in June 1923, he shot a man with a .38 pistol he had stolen from a yacht which belonged to the police chief of New Rochelle, New York.

October 1923 Panzram imprisioned at Clinton Prison, Dannemora New York

On August 12,1928 Panzram was arrested in Washington D.C. for burglary. During his interrogation, he voluntarily confessed to killing three young boys-one each in Salem, Mass and Connecticut; and a third murder Philadelphia in August 1928. The 1928 Philadelphia victim was identified as Alexander Luszock, a 14 year old newsboy; Panzram later wrote that he had also contemplated mass killings and other acts of mayhem, such as poisoning a city's water supply with arsenic, or scuttling a British warship in New York Harbor to provoke a war between the U.S. and the UK.

In light of his extensive Criminal record, he received a 25-years-to-life sentence. Upon arriving at Leavenworth Federal Penitentiary, he warned the warden, "I'll kill the first man that bothers me", and was given a solitary job in the prison laundry room. On June 20, 1929, he beat the Prison laundry foreman Robert Warnke to death with an iron bar, and was sentenced to death. He refused to allow any appeals of his sentence. In response to offers from death penalty opponents and human rights Activists to intervene, he wrote, "The only thanks you and your kind will ever get from me for your efforts on my behalf is that I wish you all had one neck and that I had my hands on it."

Panzram was hanged on September 5, 1930. As guards attempted to place a black hood over his head, he allegedly spat in the executioner's face. When asked for any last words, he responded, "Yes, hurry it up, you Hoosier bastard! I could kill a dozen men while you're screwing around!" His grave, at the Leavenworth Penitentiary Cemetery, is marked only with his prison number, 31614.

In 1938, Karl Menninger wrote Man Against Himself, including writing about Panzram using the pen name of "John Smith", with Panzram Prison Number # 31614. Lesser preserved Panzram's letters and autobiographical manuscript, then spent the next four decades in search of a publisher willing to print the material. Finally, in 1970, it was released under the title Killer: A Journal of Murder. In 1996, the book formed the basis of a film of the same name, starring James Woods as Panzram and Robert Sean Leonard as Lesser. In 1980, Lesser donated Panzram's material to San Diego State University, where they are housed, as the "Carl Panzram papers", in the Malcolm A. Love Library. In 2012, filmmaker John Borowski released a documentary entitled Carl Panzram: The Spirit of Hatred and Vengeance.

In his autobiography, Panzram wrote that he was "rage personified" and that he would often rape men whom he had robbed. He was noted for his large stature and great physical strength—due to years of hard labor at Leavenworth and other prisons—which aided him in overpowering most men he encountered. He also engaged in vandalism and arson. By his own admission, one of the few times he did not engage in Criminal activities was when he was employed as a strikebreaker against union employees. On one occasion, he tried to sign aboard as a ship's steward on an Army transport vessel, but was discharged when he reported to work intoxicated.