John Wayne Gacy Jr. was born in Chicago, Illinois, on March 17, 1942, the only son and second of three children born to John Stanley Gacy (1900–1969), an auto repair machinist and World War I veteran, and his wife Marion Elaine Robinson (1908–1989), a homemaker. Gacy was of Polish and Danish ancestry. His paternal grandparents (who spelled the family name as "Gatza" or "Gaca") had immigrated to the United States from Poland (then part of Germany). As a child, Gacy was overweight and not athletic. He was close to his two sisters and mother, but endured a difficult relationship with his father, an alcoholic who was physically abusive to his wife and children.

In 1949, Gacy's father was informed that his son and another boy had been caught sexually fondling a young girl. Gacy was whipped with a razor strop by his father as punishment. The same year, Gacy himself was ostensibly molested by a family friend, a contractor who would take Gacy for rides in his truck, then fondle him. Gacy never told his father about these incidents, afraid his father would blame him.

Although his mother, sisters, and few close friends themselves never doubted his illness, Gacy's medical condition was never conclusively diagnosed. One of Gacy's friends at school recalled several instances in which Gacy Sr. ridiculed or beat his son without provocation. On one occasion in 1957, the same friend witnessed an incident in which Gacy's father began shouting at his son for no reason, then began hitting him. Gacy's mother attempted to intervene. The friend recalled that Gacy simply "put up his hands to defend himself", adding that he never struck his father back during these altercations.

The same year Gacy became a Democratic Party candidate, his father bought him a car, with the title of the vehicle being in his father's name until Gacy had completed the monthly repayments. These repayments took several years to complete, and his father would confiscate the keys to the vehicle if Gacy did not do as his father said. On one occasion in 1962, Gacy bought an extra set of keys after his father confiscated the original set. In response, his father removed the distributor cap from the vehicle, withholding the component for three days. Gacy recalled that as a result of this incident, he felt "totally sick; drained". When his father replaced the distributor cap, Gacy left the family home and drove to Las Vegas, Nevada, where he found work within the ambulance Service before he was transferred to work as a mortuary attendant. He worked in this role for three months before returning to Chicago.

The sense of shock prompted Gacy to call his mother the next day and ask whether his father would allow him to return home. His father agreed and the same day, Gacy drove back to live with his family in Chicago. Upon his return, despite the fact he had failed to graduate from high school, Gacy successfully enrolled in the Northwestern Business College, from which he graduated in 1963. Gacy subsequently took a management trainee position within the Nunn-Bush Shoe Company.

During his courtship with Marlynn, Gacy joined the local Jaycees and became a tireless worker for the organization, being named Key Man for the organization in April 1964. The same year, Gacy had his second homosexual experience. According to Gacy, he acquiesced to this incident after one of his colleagues in the Springfield Jaycees plied him with drinks and invited him to spend the evening upon his sofa; the colleague then performed oral sex upon him while he was drunk.

By 1965, Gacy had risen to the position of vice-president of the Springfield Jaycees. The same year, he was named as the third most outstanding Jaycee within the state of Illinois.

Gacy's wife gave birth to two children: a son named Michael was born in February 1966, followed by a daughter named Christine in March 1967. Gacy himself later described this period of his life as "perfect", adding that he finally earned the long-sought approval of his father. On one occasion in July 1966, Gacy's parents paid a visit to Iowa, during which Gacy Sr. apologized privately to his son for the physical and mental abuse he had inflicted on him throughout his childhood, before proudly informing him: "Son, I was wrong about you."

On February 29, one of the youths Gacy had sexually assaulted in 1967, Donald Voorhees, testified to his ordeal at Gacy's hands, and that Gacy had subsequently paid another youth to beat him and spray Mace in his face so he would not testify against him. The youth felt unable to testify, but did briefly attempt to do so, before being asked to step down.

On the morning of March 12, william Kunkle continued to argue for the prosecution. Kunkle referred to the defense's contention of insanity as "a sham", arguing that the facts of the case hearkened to Gacy's ability to think logically and control his actions. Kunkle also referred to the testimony of a Doctor who had examined Gacy in 1968; this Doctor had diagnosed Gacy as an antisocial personality, capable of committing crimes without remorse. Kunkle indicated that had the recommendations of this Doctor been heeded, Gacy would have not been freed. At the close of his argument, Kunkle pulled each of the 22 photos of Gacy's identified victims off a board displaying the images and asked the jury not to show sympathy but to "show justice". Kunkle then asked the jury to "show the same sympathy this man showed when he took these lives and put them there!" before throwing the stack of photos into the opening of the trap door of Gacy's crawl space, which had been introduced as evidence and was on display in the courtroom. After Kunkle had finished his testimony, the jury retired to consider their verdict.

On Christmas Day 1969, Gacy's father died from cirrhosis of the liver. Gacy was not told that his father had died until two days after his death. When he heard the news, Gacy was said to have collapsed to the floor, sobbing uncontrollably, and had to be supported by prison staff. Gacy requested supervised compassionate leave from prison to attend his father's funeral in Chicago, but his request was denied.

Gacy was granted parole with 12 months' probation on June 18, 1970, after serving 18 months of his 10-year sentence. Two of the conditions of his probation were that Gacy would relocate to Chicago to live with his mother and that he was to observe a 10 p.m. curfew, with the Iowa Board of Parole receiving regular updates as to his progress.

On February 12, 1971, Gacy was charged with sexually assaulting a teenage boy. The youth claimed that Gacy had lured him into his car at Chicago's Greyhound bus terminal and driven him to his home, where he had attempted to force the youth into sex. This complaint was subsequently dismissed when the youth failed to appear in court. The Iowa Board of Parole did not learn of this incident (which violated the conditions of his parole) and eight months later, in October 1971, Gacy's parole ended. The following month, records of Gacy's previous Criminal convictions in Iowa were subsequently sealed.

On January 2, 1972, Gacy picked up 16-year-old Timothy Jack McCoy from Chicago's Greyhound bus terminal. Gacy took McCoy—who was traveling from Michigan to Omaha—on a sightseeing tour of Chicago, and then drove him to his home with the promise that he could spend the night and be driven back to the station in time to catch his bus. According to Gacy's later account of the murder, he awoke the following morning to find McCoy standing in his bedroom doorway with a kitchen knife in his hand. Gacy leapt from his bed and McCoy raised both arms in a gesture of surrender, tilting the knife upwards and accidentally cutting Gacy's forearm (Gacy had a scar on his arm to support this account). He then twisted the knife from McCoy's wrist, banged his head against his bedroom wall, kicked him against his wardrobe and walked towards him. McCoy then kicked him in the stomach and Gacy grabbed the youth, wrestled him to the floor, then stabbed him repeatedly in the chest as he straddled him with his body. Gacy claimed he then went to his kitchen and saw an opened carton of eggs and a slab of unsliced bacon on his kitchen table. McCoy had also set the table for two; he had walked into Gacy's room to wake him while absentmindedly carrying the kitchen knife in his hand. Gacy subsequently buried McCoy in his crawl space and later covered the youth's grave with a layer of concrete.

In 1973, Gacy and an employee of PDM Contractors traveled to Florida to view property Gacy had purchased. On the first night the two were alone in Florida, Gacy raped the youth in their hotel room. As a result, this youth refused to stay in the same hotel room as Gacy and instead slept on the beach. Upon returning to Chicago, this employee drove to Gacy's house as he was in his yard and beat him. Gacy's mother-in-law stopped the youth from further attacking Gacy and he drove away. Gacy explained to his wife that the attack happened because he had refused to pay the youth for poor quality work.

Gacy later stated that the second time he committed murder was around January 1974. The victim is believed to have been an unidentified teenage youth with medium brown hair estimated to be aged between 14 and 18 whom Gacy strangled before stowing the youth's body in his closet prior to burial. Gacy later stated that fluid leaked out of this youth's mouth and nose as he was stored in his closet, staining his carpet. As a result of this experience, Gacy later stated he regularly stuffed cloth rags or the victims' own underwear in their mouths to prevent a recurrence of this incident. This particular unidentified victim was buried about 15 feet (4.6 m) from the barbecue pit in Gacy's backyard.

Des Plaines police were convinced Gacy was behind Piest's disappearance and checked Gacy's record, discovering that he had an outstanding battery charge against him in Chicago and had served a prison sentence in Iowa for the sodomy of a 15-year-old boy. A search of Gacy's house on December 13 was ordered by a judge at the request of detectives and turned up several suspicious items: a 1975 high school class ring engraved with the initials J.A.S., various driver's licenses, handcuffs, a two-by-four with holes drilled in the ends, books on homosexuality and pederasty, a syringe, male clothing too small for Gacy, a 6mm Brevettata starter pistol and a photo receipt from the pharmacy where Robert Piest worked. Police decided to confiscate Gacy's Oldsmobile, along with other PDM vehicles, and assigned two two-man surveillance teams to follow Gacy, while they continued their investigation of Gacy regarding Piest's disappearance.

In May 1986, the ninth victim exhumed from Gacy's crawl space was identified as Timothy Jack McCoy, Gacy's first victim. One further victim was identified in November 2011 through DNA testing as william George Bundy, a 19-year-old construction worker who was last seen by his family on his way to a party on October 26, 1976. Bundy had apparently worked for Gacy before his murder. Shortly after Gacy's arrest, his family had contacted Bundy's dentist in the hope of submitting his dental records for comparison with the unidentified bodies. However, the records had been destroyed after the dentist had retired. A second victim was identified through DNA testing in July 2017 as a 16-year-old from Saint Paul, Minnesota named James Haakenson, who was last known to have contacted his family on August 5, 1976.

In a third case, travel records indicate Gacy was at a scheduled job site in Michigan at 6 a.m. on September 26, 1977—the day following the disappearance of a 19-year-old youth named John Mowery. Mowery was last seen leaving his mother's house at 10 p.m. on September 25. His roommate was an employee of PDM Contractors who had formerly lived with Gacy and had moved into Mowery's apartment less than one week before the youth's disappearance. Two witnesses have stated that this roommate had recommended to Mowery that he meet "a man who is going out of town" two days prior to the youth's disappearance.

Jeffrey Rignall, who had been assaulted and tortured by Gacy in March 1978, was Adam Ant that at one point during his abuse and torture, a young man with brown hair, kneeling before him, watched his abuse. When this youth realized Rignall had regained consciousness, he was again chloroformed into unconsciousness. Rignall also informed police that as Gacy was raping and assaulting him, a light was switched on in another part of the house.

On April 9, 1979, a decomposed body was discovered entangled in exposed roots on the edge of the Des Plaines River in Grundy County. The body was identified via dental records as being that of Robert Piest. A subsequent autopsy revealed that three wads of "paper-like material" had been shoved down his throat while he was alive, causing him to die of suffocation.

Gacy specifically named two employees of PDM Contractors as being the individuals he had referred to as being involved in several of the murders. In the 1980s, he also informed Robert Ressler that "two or three" employees had assisted him in several murders. Ressler replied that he believed there were unexplained avenues to the case and stated his belief that Gacy had killed more than 33 victims. Gacy neither confirmed nor denied Ressler's suspicions.

On February 15, 1983, Gacy was stabbed in the arm by Henry Brisbon, a fellow death row inmate known as the I-57 killer. At the time of the attack, Gacy had been out of his cell participating in a voluntary work program when Brisbon ran towards Gacy and stabbed him once in the upper arm with a sharpened wire. A second death row inmate injured in the attack, william Jones, received a superficial stab wound to the head. Both Gacy and Jones received treatment in the prison hospital for their wounds.

In 1984, Sam Amirante, one of Gacy's two defense attorneys at his 1980 trial, authored procedures that were incorporated by the Illinois General Assembly into the Missing Child Recovery Act of 1984. Amirante has since stated that the primary inspiration for this legislation was the fact that at the time of the Gacy murders, there had been a 72-hour period which police in Illinois had to allow to elapse before initiating a search for a missing child. The Illinois Missing Child Recovery Act of 1984 removed this 72-hour waiting period. Other states across America subsequently adopted similar procedures and sensibilities, as a result of which a national network aimed at locating missing children was gradually formed. This national network has since developed into the Child Abduction Emergency—commonly known today as an Amber Alert.

In mid-1984, the Supreme Court of Illinois upheld Gacy's conviction and ordered that he be executed by lethal injection on November 14. Gacy filed an appeal against this decision, which was denied by the Supreme Court of the United States on March 4, 1985. The following year, Gacy filed a further post-conviction petition, seeking a new trial. His then-defense Lawyer, Richard Kling, argued that Gacy had been provided with ineffective legal counsel at his 1980 trial. This post-conviction petition was dismissed on September 11, 1986.

The 1985 decision that he be executed was again appealed by Gacy, although his conviction was again upheld on September 29, 1988, with the Illinois Supreme Court setting a renewed execution date of January 11, 1989.

In the months following Gacy's execution, many of his paintings were auctioned. Some were bought so that they could be destroyed in a June 1994 communal bonfire held in Naperville, Illinois and attended by approximately 300 people, including family members of nine of Gacy's victims.

In October 2011, Cook County Sheriff Thomas Dart announced that investigators, having obtained full DNA profiles from each of the unidentified victims, were to renew their efforts to identify all of them. At a press conference held to announce this intention, Sheriff Dart stated investigators are actively seeking DNA samples from individuals across the United States related to any male missing between 1970 and 1979. Test results thus far conducted have confirmed the identification of two victims, ruled out the possibility of numerous other missing youths as being victims of Gacy, and solved four unrelated cold cases dating between 1972 and 1979.

A second request to excavate the grounds of West Miami Avenue was submitted to the Cook County State's Attorney by Sheriff Tom Dart in October 2012. This request was granted in January 2013, and a search of the property was conducted in the spring. Both FBI sniffer dogs and ground-penetrating radar equipment were used in the second search of West Miami Avenue; however, the search yielded no human remains.

In interviews following his arrest and conviction, Gacy repeatedly claimed that he was not present in Chicago when 16 of the identified victims had disappeared. In one interview, he stated that at the time of his arrest, four PDM Employees were also considered suspects in the disappearances of the missing individuals investigators had linked to Gacy—all of whom he stated were in possession of keys to his house. One of these employees was a young man named Philip Paske, who is known to have been a close associate of a man named John Norman, who operated a nationwide sex trafficking ring known as the Delta Project, which at the time operated from Chicago. At least two victims believed to have been murdered by Gacy, Kenneth Parker and Michael Marino, are known to have last been seen alive close to where Norman resided at the time of their disappearance, and Gacy is known to have been aware of Paske's connections. This led to the theory Gacy may have been connected to this trafficking ring.