Anderson began his professional career as a writer on the British crime drama comedy series El C.I.D., which ran for three series, from 1990 to 1992, and starred Alfred Molina in its first two. He met producer Jeremy Bolt and together they founded Impact Pictures in 1992, looking to raise money for Anderson’s feature film debut as director, from an action crime drama script of his own, called Shopping. After much trouble to secure funding, Shopping, which stars Sean Pertwee, Jude Law (on his first feature film role) and Sadie Frost, was released in the United Kingdom in 1994. The censors of the British Board of Film Classification were not happy with the violence of the film and delayed its release for months, hurting its commercial prospect. When it was eventually released, critics panned it and some cinemas decided to ban it for promoting an “irresponsible” outlook. In the United States it only gained an edited, direct-to-video release two years later. Anderson credits Shopping for inspiring Channel Four Films, who had financed it, to also finance the more successful Shallow Grave and Trainspotting films by Danny Boyle, which in turn, he believes, made critics reassess his film in more positive light in later years, as one of the first in a new wave of British films that concern its youth. Shopping is Anderson’s one and only British film, as he grew up watching American and mainland European movies, never seeing himself becoming a British filmmaker. Shopping was accepted in the Sundance Film Festival, which made him noticed by American studios, for the film’s look and style despite its limited $2 million budget, and opened for him the doors to Hollywood.

Anderson directed the fantasy martial arts video game adaptation Mortal Kombat in 1995, from a script written by Kevin Droney, that was based on the first couple of video games of the same name by Midway Games, and starring an ensemble cast that includes Robin Shou as Liu Kang and Christopher Lambert as Raiden. Anderson became interested in the film because he played the video game a lot at the arcades, and the producer hired him based on the accomplished visual flair of Shopping, on a very low budget. Anderson, who admits knew nothing about visual effects or fight scenes, had to study hard every book about the subject of visual effects he could find, and learned about shooting the fights while they were filming, from the more experienced people on the set, such as Shou. The film went under big reshoots to add additional fights based on feedback from screenings with fans of the video games, and it was decided to release it in August 1995, in the hopes of becoming a summer hit. While the prior video game adaptations Super Mario Bros., Double Dragon, and Street Fighter had received particularly negative reviews and bombed at the box office in the case of the first two of these films, Mortal Kombat was better received by critics, who gave it a mixed to negative reception. Critics praised the atmosphere, visuals, and fighting sequences, but criticized the plot, dialogue, and acting. The movie fared better with audiences and fans of the video games, and scored a high A- on a CinemaScore poll. As a result, the film spent three weeks as the number-one film at the US box office, earning over $122 million worldwide, on a budget of $18 million, proving to be a major success for Anderson, and becoming recognized as the first successful video game adaptation. Anderson and most cast members, including Lambert, declined to return for the sequel, Mortal Kombat: Annihilation, which, when released, was critically panned and under-performed on the box office.

The success of Mortal Kombat gave Anderson free rein to choose his next project, the science fiction action film Soldier, written by Blade Runner screenwriter David Peoples. Peoples’ script – and eventually the film itself – contains references to his work on Blade Runner, and can be considered to be taking place in the same universe, as a sidequel or standalone sequel of sorts. Kurt Russell became attached to star, but decided to take some time off to build up his body, as required by the role, which delayed the production. In the meantime, Anderson directed the 1997 science fiction horror film Event Horizon, which was written by Philip Eisner and stars Laurence Fishburne and Sam Neill. Despite attaining praise about its visuals and production design, the film was not received well by critics, or audiences (D+ on a Cinemascore poll), and failed to break even, which Anderson blamed on a tight post-production schedule and studio-enforced cuts. Event Horizon later sold well on home video and gained a small cult following. Plans to complete a director’s cut that would restore the deleted footage came to a stop when it was discovered most of it had been lost or degraded. Soldier was eventually completed and released in 1998, but was an exceptionally big critical and commercial disaster, making below $15 million in the US, on a budget of $60 million, and releasing straight-to-video in several other markets. Anderson has expressed his regret about the planned shoot on locations being changed to studio soundstages when the El Niño hurricane swooped in, which ended up compromising the film’s look. He also verbalized his disappointment with Warner Bros., who, he believes, tried to market the film to the same male teen audience as Mortal Kombat, rather than grown-up audiences, which would include women.

Anderson returned to cinema screens in 2002 with Resident Evil, a science fiction action horror film, loosely based on the video game series of the same name by Capcom. Anderson came up with the idea of adapting the games, after playing the first couple of them for days in his apartment. Because Constantin Film, who had acquired the rights to the series, were not willing to spend more money than they already had on failed attempts (including a script by George A. Romero), Anderson convinced them to write the script, titled The Undead, on spec. If they liked it, he would sell it to them as a Resident Evil film; if not, he would take it elsewhere and try to make it unrelated to the games. Anderson saw the film as a prequel of sorts to the first game in the series, and as such did not put any characters from the games in it, a fact which was criticized by fans. Instead, the film stars Milla Jovovich as an original character named Alice. Jovovich is the only actor that reprised her role in all six films of the series. In comparison to Anderson’s previous two films, Resident Evil was produced on a moderate budget of $33 million and became a commercial success of little over $100 million at the box office. The film also performed strongly on home video. Critically, Resident Evil was not received well, although, similarly to Mortal Kombat, some reviews characterized it as one of the better attempts at adapting a video game. It received the fair rating of B by audiences on a Cinemascore poll. Its relative popularity made Capcom put homages to it in video games Resident Evil 4 and Resident Evil: The Umbrella Chronicles. Anderson did not direct, but he wrote, produced, and was otherwise heavily involved with the making of two sequels, Resident Evil: Apocalypse (2004) and Resident Evil: Extinction (2007), which completed the first of the eventual two trilogies of Resident Evil films. In these two sequels, Anderson began to introduce characters from the games, albeit in supporting roles compared to Alice. Both films received similarly negative reviews to the first, but were even bigger commercial successes.

Anderson began dating Resident Evil star Milla Jovovich when they met on the 2002 film. He proposed to Jovovich in 2003, and the two were “engaged on-and-off for four years” before becoming a couple again early in 2007. On 3 November 2007, Jovovich gave birth to their first child, daughter Ever Gabo Anderson. The child was born at Cedars-Sinai Medical Center in Los Angeles, California. They married on 22 August 2009. Their second child, daughter Dashiel Edan, was born on 1 April 2015. In August 2019, Jovovich revealed that they are expecting a third daughter after losing her pregnancy two years prior. They welcomed their third daughter, Osian Lark Elliot, on 2 February 2020.

Anderson’s next project was the much-anticipated Alien vs. Predator, based on the crossover concept of the same name between the Alien and Predator franchises, which was popularized by a series of Dark Horse comics and hinted at in Predator 2. A film version had been stuck in development hell for several years, despite the franchise crossing into every other form of media, from books to comics to video games. Anderson directed the film based on a script of his own, and it was released in 2004. The film received negative reviews by critics, and a B on a Cinemascore poll by audiences. It was a big commercial success, grossing a little over $170 million, on a budget of $60 million. A sequel was made, called Aliens vs. Predator: Requiem, in which Anderson was not involved, and which failed to match Anderson’s film’s commercial or even critical performance, a fact that Anderson has used to defend his film.

After completing Alien vs. Predator, Anderson resumed work on his planned remake of Death Race 2000, which was released as Death Race in 2008. The science fiction action thriller film stars Jason Statham, and Anderson directed it based on his own screenplay. Anderson refers to it as more of a prequel than a remake on the commentary of the home video releases. The film received an average reception by critics, and scored a solid B+ on a Cinemascore poll. It grossed little over $75 million on a budget of $45 million, failing to prove a commercial success on the level of Anderson’s previous two films. Anderson wrote and produced a straight-to-video prequels, Death Race 2 (2011), and Death Race 3: Inferno (2013), which was set before the events of the 2008 film. Later, Death Race: Beyond Anarchy (2018), a sequel to the first film, in which he wrote and executive produced the film.

In 2010, Anderson wrote and directed the first installment in a second trilogy of Resident Evil films, titled Resident Evil: Afterlife. The film continues the storyline from where that last one ended. Anderson envisioned the new trilogy as a way to make use of a new stylistic approach, using slow motion and 3D. Anderson filmed in native 3D, using the Sony F35 camera, mounted on the Fusion Camera System, which was previously used in Avatar. Despite the usual negative reviews by critics, and a lukewarm B in a Cinemascore poll by audiences, the film grossed $300 million on a budget of $60 million, making over $150 million that the previously most successful film in the franchise, Resident Evil: Extinction.

Anderson wrote and directed the fifth installment in the Resident Evil film franchise, Resident Evil: Retribution, in 2012. Anderson brought back several actors from the original trilogy of films to play alternate versions of their characters. The film received generally negative reviews, and a C+ on a Cinemascore poll, the series’ lowest. Produced with a budget of $65 million, it grossed $240 million on the box office which is $60 million lower than the previous film’s gross, but still overall larger than the grosses of each films of the original trilogy.

In 2014 his 3D historical disaster romance film named Pompeii was released. Inspired by the eruption of Mount Vesuvius in 79 that destroyed Pompeii, a city of the Roman Empire, the film was written by Janet Scott Batchler, Lee Batchler and Michael Robert Johnson and stars Kit Harington, Emily Browning, Carrie-Anne Moss, Adewale Akinnuoye-Agbaje, Jessica Lucas, with Jared Harris, and Kiefer Sutherland. The film was generally negatively received by critics, and was rated a B on a Cinemascore poll. Pompeii was a modest box office success on the box office, grossing $108–118 million on a reported budget between $80 and 100 million.

In late 2016 in Japan, and early 2017 in the rest of the world, Anderson’s Resident Evil: The Final Chapter was released, which according to both him and Jovovich is the last Resident Evil film they will be involved with. Anderson designed the film “to come full circle”, provide answers to some of the series’ mysteries, and provide closure for the character of Alice. He decided to abandon the previous two films’ stylistic approach of using slow motion in favor of a more fast and gritty feeling, and he also decided to convert the film in 3D in post, instead of filming with 3D cameras. His first daughter with Jovovich, Ever Gabo Anderson, was cast in a double role, as both a young version of Alice, and the character of Red Queen introduced in the original film. The film received average to negative reviews, slightly better than the previous installments, and more along the lines of the original film. It was rated B by audiences on a Cinemascore poll, which is the highest rating in the series, and shared with the first and second films. As of 12 March 2017, it has grossed almost $307 million, on a budget of $40 million, in large part due to a record $94.3 million opening in China, making it Anderson’s highest-grossing film. Paul W. S. Anderson directed the first two episodes (with the third episode along with co-director Mark Brozel) of the science fiction television series Origin.

In 2016, Anderson was in pre-production of a feature film based on Capcom’s Monster Hunter video game franchise. Peter V. Brett’s fantasy novel The Warded Man was optioned for film production by Anderson and longtime producing partner Jeremy Bolt, but a 2016 update at Brett’s webpage stated that Anderson and Bolt are no longer involved in the film production.