In 1914, German American immigrant Carl Laemmle bought the Taylor Ranch in the San Fernando Valley and founded Universal City as a gigantic studio with its own zoo, its own police and mayor and Native Americans living on the premises. On March 14, 1915, Laemmle opened Universal Studios in a two-day grand opening event with 10,000 attendees. He later invited the general public to see all the action for an admission fee of just five cents, which also included a boxed lunch with chicken. There was also a chance to buy fresh produce, since then-rural Universal City was still in part a working farm. This original tour was discontinued around 1930, due to the advent of sound films and the stages being not sufficiently soundproofed.

Universal Studios Hollywood's backlot has been damaged by fire nine times throughout its history. The first was in 1932, when embers from a nearby brush fire were blown toward the back lot, causing four movie sets to be destroyed and resulting in over $100,000 damage. Seventeen years later, in 1949, another brush fire caused the complete destruction of one building and damage to two others. In 1957, the New York street film studio set was destroyed by an arson fire, causing a half-million dollars in damage. Ten years later, in 1967, twice as much damage was done when the Little Europe area and part of Spartacus Square was destroyed. It also destroyed the European, Denver and Laramie street sets. In 1987, the remaining portion of Spartacus Square was destroyed along with street sets and other buildings. As with the 1957 fire, this was suspected to be the result of an arsonist. Just three years later, another fire was deliberately started in the back lot. The New York Street set, the Ben Hur set and the majority of Courthouse Square were destroyed. In 1997, the seventh fire occurred at the back lot. A portion of Courthouse Square was again destroyed, though most survived.

The most damage was done on June 1, 2008 when a three alarm fire broke out on the back lot of Universal Studios. The fire started when a worker was using a blowtorch to warm asphalt shingles being applied to a facade. The Los Angeles County Fire Department had reported that Brownstone Street, New York Street, New England Street, the King Kong attraction, some structures that make up Courthouse Square, and the Video Vault had burned down (not to be confused with the actual Film Vault; the Video Vault contains duplicates of Universal's film library). Aerial news footage captured the Courthouse building surviving fire for the third time in its history, with only the west side of it being slightly charred. Over 516 firefighters from various local fire departments, as well as two helicopters dropping water, had responded to the fire. Fourteen firefighters and three Los Angeles County sheriffs' deputies sustained minor injuries. The fire was put out after twelve hours, during which time firefighters encountered low water pressure.

Destroyed were 40,000 to 50,000 archived digital video and film copies chronicling Universal's movie and television show history, dating back to the 1920s, including the films Knocked Up and Atonement, the NBC series Law & Order, The Office, and Miami Vice, and CBS's I Love Lucy.

Universal president Ron Meyer stated "Nothing irreplaceable was lost. We have duplicates of everything that was lost."

Several days after the fire, it was reported that the King Kong attraction would not be rebuilt and would eventually be replaced by a new attraction that had yet to be announced. In August 2008, Universal changed its position and announced plans to rebuild the King Kong attraction, basing the new attraction on the 2005 film adaptation.

It emerged only in June 2019, in an article published by The New York Times that the fire had totally destroyed Building 6197, a warehouse adjoining the King Kong attraction, which housed a video vault and, significantly, a huge archive of analog audio master tapes belonging to Universal Pictures' former division the Universal Music Group (UMG). The collection included the master tape catalogues of various labels acquired by Universal over the years, including Chess, Decca, MCA, Geffen, Interscope, A&M, Impulse, and a host of subsidiary labels. Estimates of the individual items lost range from 118,000 to 175,000 album and 45rpm single master tapes, gramophone master discs, lacquers and acetates, as well as all the documentation contained in the tape boxes. Many of the tapes destroyed contained unreleased recordings such as outtakes, alternate versions of released material, and instrumental 'submaster' multitracks created for subsequent dubbing and mixdown to the final master tape. Randy Aronson, who was manager of the vault at the time of the fire, estimates that as many as 500,000 individual song titles were lost.

Among the losses were all of Decca's masters from the 1930s to the 1950s and most of the original Chess masters which included artists such as Chuck Berry, Otis Redding, Muddy Waters and Howlin' Wolf, and most of the John Coltrane's master tapes from his later career on Impulse Records; the Chess, Coltrane and Impulse Records recordings were later confirmed to have survived. In a statement issued on June 11, 2019, UMG disputed The New York Times article saying it contained "numerous inaccuracies", as well as "fundamental misunderstandings of the scope of the incident and affected assets," but was unable to publicly disclose details due to "constraints".

Following the publication of the New York Times story, Questlove of The Roots confirmed that the master tapes for two of the band's albums, including unused material and multi-track recordings, were lost in the fire. Similarly, Nirvana bassist Krist Novoselic said he believed the masters for the band's 1991 album Nevermind were "gone forever" as a result of the fire. Representatives for R.E.M. announced they would investigate the effects the fire may have had on the band's archival materials, while Hole, Steely Dan, Rosanne Cash and Geoff Downes made statements on their possible losses from the fire.

A representative for Eminem confirmed that the rapper's master recordings were digitized months before the fire, but did not confirm whether the physical master reels of his recordings were affected. UMG archivist Patrick Kraus assured that the Impulse Records, John Coltrane, Muddy Waters, Ahmad Jamal, Nashboro Records, and Chess Records masters survived the fire and were still in Universal's archive.

Shortly after Music Corporation of America (MCA) took over Universal Pictures in 1962, accountants suggested a new tour in the studio commissary would increase profits. On July 15, 1964, the modern tour was established to include a series of dressing room walk-throughs, peeks at actual production, and later, staged events. This grew over the years into a full-blown theme park. The narrated tram tour (formerly "Glamor Trams") still runs through the studio's active backlot, but the staged events, stunt demonstrations and high-tech rides overshadow the motion-picture production that once brought fans to Universal Studios Hollywood.

In 1965, the War Lord Tower opened as one of the first attractions in the theme park. One of the early struggles for Universal was coming up with things for young children to do. The existing small Ma & Pa Kettle Petting Zoo was expanded into the Ark Park. This area encompassed the Mt. Ararat petting zoo with over 200 animals and birds representing 30 species and a Noah's Nursery and a Noah's Love Inn playhouse for children and animals. This was followed by the opening of the Animal Actors' School Stage in 1970. In 1968, the Screen Actors Guild enacted a rule prohibiting visitors from most soundstages. This new rule, coupled with more productions being shot on location, meant the backlot tram tour could not show visitors much in the way of real movie and television production. Jay Stein, President of the Recreation Division, championed the idea of creating exciting experiences for visitors in place of viewing actual production. Later that same year, the Flash Flood set was opened and this first special-effects attraction proved to be a hit. 20,000 gallons of water rushed 200 feet down a narrow Mexican village street, uprooting an old tree and threatening to engulf the tram. The Parting of the Red Sea attraction opened in 1973. In 1974, the Rockslide staged event was added to the Studio Tour. The following year, The Land of a Thousand Faces opened on the Upper Lot. In 1979, the Battle of Galactica replaced Rockslide as a staged event on the Studio Tour. In 1989's The Wizard, it was the site of the fictional Video Armageddon competition which gave way to the Nintendo World Championships held in 1990.

The Flintstones Show opened, replacing the Star Trek Adventure. In 1991, E.T. Adventure opened as the park's first "dark ride," an industry term for an attraction that uses ride vehicles to take passengers through an indoor show building. Around the same time, sister park Universal Studios Florida opened, which had its own, similar E.T. attraction. The Florida version was more of a conventional theme park and paved the way for the Hollywood park's evolution. In 1993, Back to the Future: The Ride replaced Battle of Galactica. In 1996, Jurassic Park: The Ride opened. In 1997, The Land Before Time show replaced Rocky and Bullwinkle Live only to be replaced with Coke Soak a year later, and Totally Nickelodeon replaced the Flintstones Show. In 1999, T2-3D: Battle Across Time and a Chicken Run Walkthrough opened on the Upper Lot, and Beetlejuice's Rock and Roll Graveyard Revue was closed.

In 2000, the Rugrats Magic Adventure replaced Totally Nickelodeon. In 2001, the Nickelodeon Blast Zone opened, and Animal Planet Live replaced the Animal Actors' School Stage. In 2003, E.T. Adventure was closed to make way for Revenge of the Mummy, which opened in 2004. This was the first roller coaster to open at the park. The following year, Fear Factor Live replaced Spider-Man Rocks. In 2007, Universal's House of Horrors replaced Van Helsing: Fortress Dracula. Both Back to the Future: The Ride and Lucy: A Tribute were closed, being replaced in 2008 by The Simpsons Ride and the Universal Story Museum respectively. Also in 2008, the Nickelodeon Blast Zone was re-branded to the Adventures of Curious George. In 2009, Creature from the Black Lagoon: The Musical replaced Fear Factor Live in the Upper Lot.

In 2010, the Special Effects Stages and Backdraft attractions were closed to make way for Transformers: The Ride – 3D, which was announced in 2008; Special Effects Stages moved to the former Creature From The Black Lagoon building and removed the last "s" from its name. King Kong 360 3-D also opened. On May 24, 2012, Transformers: The Ride – 3D opened on the Lower Lot. On December 31, 2012, Universal Studios Hollywood closed T2-3D: Battle Across Time for Despicable Me Minion Mayhem, which opened in 2014.

In April 2014, the park announced Springfield, a new dining complex to be built around the Simpsons Ride. The new eateries feature "signature eateries from Krusty Burger to Luigi's Pizza and Phineas Q. Butterfat's 5,600 Flavors Ice Cream Parlor to iconic watering holes like Moe's Tavern and Duff's Brewery". It opened on March 28, 2015.

On May 7, 2015, Universal Studios announced it formed a partnership with Nintendo to create attractions and merchandise based on Mario and other Nintendo characters. The following year, the area was called "Super Nintendo World", and was confirmed that it would come to Universal Studios Japan in 2020 as well as Universal Orlando and Universal Studios Hollywood later on.

On August 13, 2017, Shrek 4-D closed after 14 years to make way for the DreamWorks Theatre. In 2018, Jurassic Park: The Ride was closed and refurbished into Jurassic World: The Ride, which opened in 2019.

On April 10, 2019, the park announced The Secret Life of Pets: Off the Leash!, an attraction based on The Secret Life of Pets. The attraction was set to open on March 27, 2020, adjacent to the Despicable Me Minion Mayhem attraction. However, Universal announced a temporary closure starting on March 14, 2020 to combat the COVID-19 pandemic. On March 5, 2021, it was announced that Universal Studios Hollywood could reopen with reduced capacity beginning April 1, 2021. At the end of March, it was announced that the park would reopen to California residents on April 16, 2021. Universal also announced that The Secret Life of Pets: Off the Leash! ride would be open to the public on that day, together with a new, fully articulated version of the Indominus Rex in Jurassic World: The Ride.

On March 10, 2022, Universal Studios Hollywood announced that its version of Super Nintendo World would open in 2023. On December 14, 2022, Universal officially announced that the land would open in Hollywood on February 17, 2023. The area soft-opened under technical rehearsals for reserved-guests on January 12, and officially opened as planned on February 17, about a month and a half before the release of Universal/Illumination's The Super Mario Bros. Movie.

On July 12, 2023, it was announced that a Fast & Furious-themed roller coaster was being built. In May 2024, the coaster was revealed as Fast & Furious: Hollywood Drift, with an expected opening in 2026.