Joaquín Archivaldo Guzmán Loera was born into a poor family in the rural community of La Tuna, Badiraguato, Sinaloa, Mexico. Sources disagree on the date of his birth, with some stating he was born on 25 December 1954, while others report he was born on 4 April 1957. His parents were Emilio Guzmán Bustillos and María Consuelo Loera Pérez. His paternal grandparents were Juan Guzmán and Otilia Bustillos, and his maternal grandparents were Ovidio Loera Cobret and Pomposa Pérez Uriarte. For many generations, his family lived and died at La Tuna. His Father was officially a cattle rancher, as were most in the area where Guzmán grew up; according to some sources, however, he may have possibly also been a gomero, a Sinaloan word for opium poppy farmer. Guzmán has two younger sisters, Armida and Bernarda, and four younger brothers: Miguel Ángel, Aureliano, Arturo and Emilio. He had three unnamed older brothers who reportedly died of natural causes when he was very young.

Throughout most of the late 1970s and early 1980s, the Mexican drug traffickers were also middlemen for the Colombian trafficking groups, and would transport their cocaine through the U.S.-Mexico border and receive a fee for each kilogram. Mexico, however, remained a secondary route for the Colombians, given that most of the drugs trafficked by their cartels were smuggled through the Caribbean and the Florida corridor. Félix Gallardo was the leading drug baron in Mexico and friend of Juan Ramón Matta-Ballesteros, but his operations were still limited by his counterparts in South America. In the mid-1980s, however, the U.S. government increased law enforcement surveillance and put pressure on the Medellín and Cali Cartels by effectively reducing the drug trafficking operations in the Caribbean corridor. Realizing it was more profitable to hand over the operations to their Mexican counterparts, the Colombian cartels gave Félix Gallardo more control over their drug shipments. This power shift gave the Mexican organized crime groups more leverage over their Central American and South American counterparts. During the 1980s, however, the Drug Enforcement Administration (DEA) was conducting undercover groundwork in Mexico, where several of its agents worked as informants.

In 1977, Guzmán married Alejandrina María Salazar Hernández in a small ceremony in the town of Jesús María, Sinaloa. They had at least three children: César, Iván Archivaldo, and Jesús Alfredo. He set them up in a ranch home in Jesús María.

In the mid-1980s, Guzmán married once more, to Griselda López Pérez, with whom he had four more children: Édgar, Joaquín, Ovidio, and Griselda Guadalupe.

One DEA agent, Enrique Camarena Salazar, was working as an informant and grew close to many top drug barons, including Félix Gallardo. In November 1984, the Mexican military—acting on the intelligence information provided by Camarena—raided a large marijuana plantation owned by the Guadalajara Cartel and known as "Rancho Búfalo". Angered by the suspected betrayal, Félix Gallardo and his men exacted revenge when they kidnapped, tortured, and killed Camarena in February 1985. The death of Camarena outraged Washington, and Mexico responded by carrying out a massive manhunt to arrest those involved in the incident. Guzmán took advantage of the internal crisis to gain ground within the cartel and take over more drug trafficking operations. In 1989, Félix Gallardo was arrested; while in prison and through a number of envoys, the drug lord called for a summit in Acapulco, Guerrero. In the conclave, Guzmán and others discussed the Future of Mexico's drug trafficking and agreed to divide the territories previously owned by the Guadalajara Cartel. The Arellano Félix brothers formed the Tijuana Cartel, which controlled the Tijuana corridor and parts of Baja California; in Chihuahua state, a group controlled by Carrillo Fuentes family formed the Juárez Cartel; and the remaining faction left to Sinaloa and the Pacific Coast and formed the Sinaloa Cartel under the traffickers Ismael "El Mayo" Zambada, Palma, and Guzmán. Guzmán was specifically in charge of the drug corridors of Tecate, Baja California, and Mexicali and San Luis Río Colorado, two border crossings that connect the states of Sonora and Baja California with the U.S. states of Arizona and California.

When Félix Gallardo was arrested, Guzmán reportedly lived in Guadalajara, Jalisco for some time. One of his other centers of operation, however, was in the border city of Agua Prieta, Sonora, where he coordinated drug trafficking activities more closely. Guzmán had dozens of properties in various parts of the country. People he trusted purchased the properties for him and registered them under false names. Most of them were located in residential neighborhoods and served as stash houses for drugs, weapons, and cash. Guzmán also owned several ranches across Mexico, but most of them were located in the states of Sinaloa, Durango, Chihuahua, and Sonora, where locals working for the drug lord grew opium and marijuana. The first time Guzmán was detected by U.S. authorities for his involvement in organized crime was in 1987, when several protected witnesses testified in a U.S. court that Guzmán was in fact heading the Sinaloa Cartel. An indictment issued in the state of Arizona alleged that Guzmán had coordinated the shipment of 2,000 kg (4,400 lb) of marijuana and about 4,700 kg (10,400 lb) of cocaine from 19 October 1987 to 18 May 1990, and had received roughly US$1.5 million in drug proceeds that were shipped back to his home state. Another indictment alleged that Guzmán earned US$100,000 for trafficking 70,000 lb (roughly 31,750 kg) of cocaine and an unspecified amount of marijuana in a period of three years. In the border areas between Tecate and San Luis Río Colorado, Guzmán ordered his men to traffic most of the drugs overland, but also through a few aircraft. By using the so-called piecemeal strategy, in which traffickers kept drug quantities relatively low, risks were reduced. Guzmán also pioneered the use of sophisticated underground tunnels to move drugs across the border and into the United States. Aside from pioneering the tunnels, Palma and Guzmán packed cocaine into chili pepper cans under the brand "La Comadre" before they were shipped to the U.S. by train. In return, the drug lords were paid through large suitcases filled with millions of dollars in cash. These suitcases were flown from the U.S. to Mexico City, where corrupt customs agents at the airport made sure the deliveries were not inspected. Large sums of that money were reportedly used as bribes for members of the Attorney General's Office.

When Félix Gallardo was arrested, the Tijuana corridor was handed over to the Arellano Félix brothers, Jesús Labra Áviles (alias "El Chuy"), and Javier Caro Payán (alias "El Doctor"), cousin of the former Guadalajara Cartel leader Rafael Caro Quintero. In fears of a coup, however, Caro Payán fled to Canada and was later arrested. Guzmán and the rest of the Sinaloa Cartel Leaders consequently grew angry at the Arellano Félix clan about this. In 1989, Guzmán sent Armando López (alias "El Rayo"), one of his most trusted men, to speak with the Arellano Félix clan in Tijuana. Before he had a chance to speak face-to-face with them, López was killed by Ramón Arellano Félix. The corpse was disposed of in the outskirts of the city and the Tijuana Cartel ordered a hit on the remaining members of the López family to prevent Future reprisals. That same year, the Arellano Félix brothers sent the Venezuelan drug trafficker Enrique Rafael Clavel Moreno to infiltrate Palma's family and seduce his wife Guadalupe Leija Serrano. After convincing her to withdraw US$7 million from one of Palma's bank accounts in San Diego, California, Clavel beheaded her and sent her head to Palma in a box. It was known as the first beheading linked to the drug trade in Mexico. Two weeks later, Clavel killed Palma's children, Héctor (aged 5) and Nataly (aged 4), by throwing them off a bridge in Venezuela. Palma retaliated by sending his men to kill Clavel while he was in prison. In 1991, Ramón killed another Sinaloa Cartel associate, Rigoberto Campos Salcido (alias "El Rigo"), and prompted bigger conflicts with Guzmán. In early 1992, a Tijuana Cartel-affiliated and San Diego-based gang known as Calle Treinta kidnapped six of Guzmán’s men in Tijuana, tortured them to obtain information, and then shot them in the back of their heads. Their bodies were dumped on the outskirts of the city. Shortly after the attack, a car bomb exploded outside one of Guzmán’s properties in Culiacán. No injuries were reported, but the drug lord became fully aware of the intended message.

Guzmán and Palma struck back against the Arellano Félix brothers (Tijuana Cartel) with nine killings on 3 September 1992 in Iguala; among the dead were lawyers and family members of Félix Gallardo, who was also believed to have orchestrated the attack against Palma's family. Mexico's Attorney General formed a special unit to look into the killings, but the investigation was called off after the unit found that Guzmán had paid off some of the top police officials in Mexico with $10 million, according to police reports and confessions of former police officers. In November 1992, gunmen of Arellano Félix attempted to kill Guzmán as he was traveling in a vehicle through the streets of Guadalajara. Ramón and at least four of his henchmen shot at the moving vehicle with AK-47 rifles, but the drug lord managed to escape unharmed. The attack forced Guzmán to leave Guadalajara and live under a false name under fears of Future attacks. He and Palma, however, responded to the assassination attempt in a similar fashion; several days later, on 8 November 1992, a large number of Sinaloa Cartel men posing as policemen stormed the Christine discothèque in Puerto Vallarta, spotted Ramón and Francisco Javier Arellano Félix, and opened fire at them. The shooting lasted for at least eight minutes, and more than 1,000 rounds were fired by both Guzmán's and Arellano Félix's gunmen. Six people were killed in the shootout, but the Arellano Félix brothers were in the restroom when the raid started and reportedly escaped through an air-conditioning duct before leaving the scene in one of their vehicles. On 9 and 10 December 1992, four alleged associates of Félix Gallardo were killed. The antagonism between Guzmán's Sinaloa Cartel and the Arellano Félix clan left several more dead and was accompanied by more violent events in the states of Baja California, Sonora, Sinaloa, Durango, Jalisco, Guerrero, Michoacán and Oaxaca.

This became a key factor influencing the break between the Sinaloa Cartel and the Beltrán Leyva brothers, five brothers who served as Guzmán's top lieutenants, primarily working for the cartel in the northern region of Sinaloa. Sinaloa Lawyer Loya-Castro, who like Guzmán had been wanted on federal charges in the United States since 1993, voluntarily approached the DEA offering them information in 1998, eventually signing paperwork as a formal informant in 2005, and his U.S. indictment was thrown out in 2008. Loya-Castro's leaks to the DEA led to the dismantling of the Tijuana Cartel, as well as the Mexican Army's arrest of Guzmán's lieutenant and the top commander of the Beltrán Leyva organization, Alfredo Beltrán Leyva (also known as El Mochomo, or "Desert Ant"), in Culiacán in January 2008, with Guzmán believed to have given up El Mochomo for various reasons. Guzmán had been voicing concerns with Alfredo Beltrán's lifestyle and high-profile actions for some time before his arrest. After El Mochomo's arrest, authorities said he was in charge of two hit squads, money laundering, transporting drugs and bribing officials.

When Palma was arrested by the Mexican Army on 23 June 1995, Guzmán took leadership of the cartel. Palma was later extradited to the United States, where he is in prison on charges of drug trafficking and conspiracy.

While still in prison in Mexico, Guzmán was indicted in San Diego on U.S. charges of money laundering and importing tons of cocaine into California, along with his Sinaloa attorney Humberto Loya-Castro, or Licenciado Perez ("Lawyer Perez"), who was charged with bribing Mexican officials on Sinaloa's behalf and making sure that any cartel members arrested were released from custody. After a ruling by the Supreme Court of Mexico made extradition between Mexico and the United States easier, Guzmán bribed guards to aid his escape. On 19 January 2001, Francisco "El Chito" Camberos Rivera, a prison guard, opened Guzmán's electronically operated cell door, and Guzmán got into a laundry cart that maintenance worker Javier Camberos rolled through several doors and eventually out the front door. He was then transported in the trunk of a car driven by Camberos out of the town. At a gas station, Camberos went inside, but when he came back, Guzmán was gone on foot into the night. According to officials, 78 people have been implicated in his escape plan. Camberos is in prison for his assistance in the escape.

After Guzmán's prison escape nearly a decade after his initial arrest, he and close associate Ismael Zambada García became Mexico's undisputed top drug kingpins after the 2003 arrest of their rival Osiel Cárdenas of the Gulf Cartel. Until Guzmán's arrest in 2014, he was considered the "most powerful drug trafficker in the world" by the United States Department of the Treasury. Guzmán also had another close associate, his trusted friend Ignacio "Nacho" Coronel Villarreal.

Since his 2001 escape from prison, Guzmán had been wanting to take over the Ciudad Juárez crossing points, which were under the control of the Carrillo Fuentes family of the Juárez Cartel. Despite a high degree of mistrust between the two organizations, the Sinaloa and Juárez cartels had a working agreement at the time. Guzmán convened a meeting in Monterrey with Ismael Zambada García ("El Mayo"), Juan José Esparragoza Moreno ("El Azul") and Arturo Beltrán Leyva. In this meeting, they discussed killing Rodolfo Carrillo Fuentes, who was in charge of the Juárez Cartel at the time. On 11 September 2004, Rodolfo, his wife and two young children were visiting a Culiacán shopping mall. While leaving the mall, escorted by police commander Pedro Pérez López, the family was ambushed by members of Los Negros, assassins for the Sinaloa Cartel. Rodolfo and his wife were killed; the policeman survived.

On 15 February 2005, Guzmán's son Iván Archivaldo, known as "El Chapito", was arrested in Guadalajara on money laundering charges. He was sentenced to five years in a federal prison but released in April 2008, after a Mexican federal judge, Jesús Guadalupe Luna, ruled that there was no proof his cash came from drugs other than that he was a drug lord's son. Luna and another judge were later suspended on suspicion of unspecified irregularities in their decisions, including Luna's decision to release "El Chapito".

Obied was a brother of Luis Alberto Cano Zepeda (alias "El Blanco")'s, another nephew of Guzmán's who worked as a pilot drug transporter for the Sinaloa cartel. The latter was arrested by the Mexican military in August 2006. InSight Crime notes that Obied's murder may have been either a retaliation attack by Los Zetas, for Guzmán's incursions into their territory, or a brutal campaign heralding Los Zetas' presence in Sinaloa.

In November 2007, Guzmán married an 18-year-old American beauty queen, Emma Coronel Aispuro, the daughter of one of his top deputies, Inés Coronel Barreras, in Canelas, Durango. In August 2011, she gave birth to twin girls, Maria Joaquina and Emali Guadalupe, in Los Angeles County Hospital, in California.

Guzmán's son Édgar Guzmán López died after a 2008 ambush in a shopping center parking lot, in Culiacán, Sinaloa. Afterwards, police found more than 500 AK-47 bullet casings (7.62×39mm) at the scene. Guzmán's brother Arturo, known as "El Pollo", was killed in prison in 2004.

Each year from 2009 to 2011, Forbes magazine ranked Guzmán as one of the most powerful people in the world, ranking him 41st, 60th, and 55th, respectively. He was thus the second most powerful man in Mexico, after Carlos Slim. The magazine also calls him the "biggest drug lord of all time." The U.S. federal government considers Joaquin Guzmán "The most ruthless, dangerous, and feared man on the planet" and the U.S. Drug Enforcement Administration (DEA) estimated he matched the influence and reach of Pablo Escobar, and considered him "the godfather of the drug world". In 2013, the Chicago Crime Commission named Guzmán "Public Enemy Number One" for the influence of his Criminal network in Chicago, though there is no evidence that Guzmán has ever been in that city. The last person to receive such notoriety was Al Capone in 1930.

Guzmán's sons followed him into the drug Business, and his third wife, López Pérez, was arrested in 2010, in Culiacán.

His drug empire made him a Billionaire, and he was ranked as the 10 richest man in Mexico and 1,140th in the world in 2011, with a net worth of roughly US$1 billion. To assist his drug trafficking, the Sinaloa Cartel also built a shipping and transport empire. Guzmán has been referred to as the "biggest drug lord of all time", and the U.S. DEA considered him "the godfather of the drug world" and strongly estimates he surpassed the influence and reach of Pablo Escobar. In 2013, the Chicago Crime Commission named Guzmán "Public Enemy Number One" for the influence of his Criminal network in Chicago (there is no evidence that Guzmán has ever been in that city, however.) The last person to receive such notoriety was Al Capone in 1930.

On the night of 17 June 2012, Obied Cano Zepeda, a nephew of Guzmán's, was gunned down by unknown assailants at his home in the state capital of Culiacán, while hosting a Father's Day celebration. The gunmen, who were reportedly carrying AK-47 rifles, also killed two other guests and left another seriously injured.

On 1 May 2013, Guzmán's father-in-law, Inés Coronel Barreras, was captured by Mexican authorities in Agua Prieta, Sonora, with no gunfire exchanged. U.S. authorities believe Coronel Barreras was a "key operative" of the Sinaloa Cartel who grew and smuggled marijuana through the Arizona border area.

On 11 November 2014, a federal court in Sinaloa granted Guzmán an injunction for weaponry charges after the judge determined that the arrest was not carried out the way the Mexican Navy reported it. According to law enforcement, the Navy apprehended Guzmán after they received an anonymous tip on an armed individual in the hotel where he was staying. However, no evidence of the anonymous tip was provided. The judge also determined that the investigations leading to his arrest were not presented in court. He determined that law enforcement's version of the arrest had several irregularities because the Navy did not have a raid warrant when they entered the premises and arrested Guzmán (when he was not the subject matter of the anonymous tip in the first place).

Mexican authorities raided 18 known Guzmán residences in the months before his capture. Guzmán had a close call in early October 2015, several days after meeting with American actor Sean Penn and Mexican Actress Kate del Castillo. The Actress was first approached by Guzmán's lawyers in 2014, after having published an open letter to Guzmán in 2012 in which she expressed her sympathy and requested him to "traffic in love" instead of in drugs; Guzmán reached out again to del Castillo after his 2015 escape, and allegedly sought to cooperate with her in making a film about his life. On 2 October, Penn and del Castillo visited Guzmán for seven hours at his hideout in the mountains, with Penn interviewing the fugitive for Rolling Stone magazine. Guzmán, who had never before acknowledged his drug trafficking to a Journalist, told Penn he had a "fleet of submarines, airplanes, trucks and boats" and that he supplied "more heroin, methamphetamine, cocaine and marijuana than anybody else in the world". An unnamed Mexican official confirmed that Penn's meeting helped authorities locate Guzmán, with cell phone interceptions and information from American authorities directing Mexican Marines to a ranch near Tamazula, Durango, in the Sierra Madre mountains in western Mexico. The raid on the ranch was met with heavy gunfire and Guzmán was able to flee. The Attorney General of México declared that "El Chapo ran away through a gully and, although he was found by a helicopter, he was with two women and a girl and it was decided not to shoot". The two women were later revealed to be Guzmán's personal chefs, who had traveled with him to multiple safe houses. At one point, Guzmán reportedly carried a child on his arms "obscuring himself as a target".

Guzmán was transferred on 5 May 2016 to a prison near Ciudad Juarez, near the border with Texas. At that point, Mexico expected to extradite Guzmán to the United States by February 2017.

In 2017, Netflix and Univision began co-producing the series, El Chapo, about the life of Guzmán. The series premiered on Sunday, 23 April 2017 at 8PM/7C on Univision and was followed by a 20-minute Facebook Live after-show titled "El Chapo Ilimitado".

U.S. District Judge Brian Cogan has scheduled the trial of Guzman for September 2018. Meanwhile, Guzman's Lawyer, Eduardo Balarezo, warned that keeping the jurors' identity secret is not necessary for their safety, and it would jeopardize a fair trial by implying that Guzman is dangerous and guilty. According to the prosecutors, juror's anonymity and an armed escort are necessary even if Guzman is in isolation, due to his history of having jurors and witnesses killed. The judge agreed to keep the jurors' anonymity and also to be transported to and from the courthouse by US Marshals and sequestered from the public while in the courthouse.

Although Guzmán had long hidden successfully in remote areas of the Sierra Madre mountains, the arrested members of his security team told the military he had begun venturing out to Culiacán and the beach town of Mazatlán. A week before his capture, Guzmán and Zambada were reported to have attended a family reunion in Sinaloa. The Mexican military followed the bodyguards' tips to Guzmán’s former wife's house, but they had trouble ramming the steel-reinforced front door, which allowed Guzmán to escape through a system of secret tunnels that connected six houses, eventually moving south to Mazatlán. He had planned to stay a few days in Mazatlán to see his twin baby daughters before retreating to the mountains.