C.K. was born Louis A. Székely in Washington, D.C. on September 12, 1967, the son of software Engineer Mary Louise (née Davis) and Economist Luis Székely. His parents met at Harvard University, where his mother was completing her degree in a summer school program. They were married at St. Francis Church in Traverse City, Michigan. C.K. has three sisters. His paternal grandfather, Dr. Géza Székely Schweiger, was a Hungarian Jewish surgeon whose family moved to Mexico, where he met C.K.'s Mexican paternal grandmother, Rosario Sánchez Morales. C.K.'s mother, an American with Irish ancestry, grew up on a farm in Michigan. She graduated from Owosso High School in Owosso, Michigan. She attended University of Michigan and graduated from Ohio State University Phi Beta Kappa. C.K.'s maternal grandparents were M. Louise Davis and Alfred C. Davis.

In 1984, C.K. at 17 directed the comedic short film Trash Day. The New York University Tisch School of the Arts showed an interest in him as a filmmaker, but he instead decided to pursue a career in stand-up comedy. C.K.'s first attempt at stand-up was in 1985 at an open mic night at a comedy club in Boston, Massachusetts, during the apex of the comedy boom. He was given five minutes of time, but had only two minutes of material. He was so discouraged by the experience that he did not perform again for two years. He and Marc Maron later reminisced about their early careers and friendship on Maron's WTF Podcast. As Boston's comedy scene grew, C.K. gradually achieved success, performing alongside acts such as Denis Leary and Lenny Clarke, and eventually he moved up to paid gigs, opening for Jerry Seinfeld and hosting comedy clubs until he moved to Manhattan in 1989. He performed his act on many televised programs, including Evening at the Improv and Star Search. C.K.'s short film Ice Cream (1993), was submitted to the Aspen Shortsfest in 1994.

C.K. attended Newton North High School, and graduated in 1985. He graduated with Future Friends star Matt LeBlanc. After graduation, C.K. worked as an auto mechanic and at a public access TV cable station in Boston. According to C.K., working in public access TV gave him the tools and technical knowledge to make his short films and later his television shows. "Learning is my favorite thing", he said. He also worked for a time as a cook and in a video store.

C.K. began his career in the 1990s and early 2000s writing for comedians including David Letterman, Conan O'Brien, Dana Carvey, Chris Rock, and also for other comedy shows. Also in this period, he was directing surreal short films and went on to direct two features—Tomorrow Night (1998) and Pootie Tang (2001). In 2001, C.K. released his debut comedy album, Live in Houston directly through his website and became among the first performers to offer direct-to-fan sales of tickets to his stand-up shows, as well as DRM-free video concert downloads, via his website. He has released nine comedy albums, often directing and editing his specials as well. He had supporting acting roles in the films The Invention of Lying (2009), American Hustle, Blue Jasmine (both 2013), and Trumbo (2015). C.K. created, directed, executive produced, starred in, wrote, and was the primary Editor of, Louie, an acclaimed semi-autobiographical comedy-drama series aired from 2010 to 2015 on FX. In 2016, C.K. created and starred in his self-funded web series Horace and Pete. He also co-created the shows Baskets and Better Things for FX and voiced Max the dog in the animated film The Secret Life of Pets in the same year. His 2017 film, I Love You, Daddy, was pulled from distribution prior to its scheduled release date after multiple women accused him of sexual harassment.

In 1993, he unsuccessfully auditioned for Saturday Night Live, although he did, however, later work with Robert Smigel on the TV Funhouse shorts for the program. C.K.'s earliest writing job was for Conan O'Brien on the late-night talk show Late Night with Conan O'Brien from 1993 to 1994, before briefly writing for Late Show with David Letterman in 1995. C.K. and Artist Alix Bailey married in 1995. Together, they had two daughters. Throughout the spring of 1996, C.K. served as the head Writer for The Dana Carvey Show; its Writers also included Steve Carell, Stephen Colbert, Robert Smigel, and Charlie Kaufman. It was cancelled after seven episodes. In 1996, HBO released his first half-hour comedy special. From 1997 to 1999, he wrote for The Chris Rock Show. His work for on the show was nominated for a Primetime Emmy Award for writing three times, winning "Best Writing in a Variety or Comedy Series" in 1999. He was also nominated for an Emmy for his work writing for Late Night with Conan O'Brien. He has been quoted as describing his approach to writing as a "deconstruction" that is both painful and frightening.

In 1998, C.K. wrote and directed the independent black-and-white film Tomorrow Night, which premiered at Sundance, marking his feature film directorial debut after making several shorter films, including six short films for the Sketch comedy show Howie Mandel's Sunny Skies (1995) on the Showtime cable network. C.K. self-released Tomorrow Night in 2014. He hosted the PBS show ShortCuts in 1999, which featured independent short films, including some made by C.K. himself. Also that year, C.K. devised and starred in The Filthy Stupid Talent Show, a mock talent show television special. He had an early acting role in the independent comedy Tuna, alongside Nick Offerman, in 2000 and performed on the stand-up showcase series Comedy Central Presents the following year.

Upon moving from Mexico to suburban Boston, C.K. wanted to become a Writer and Comedian, citing Richard Pryor, Steve Martin, and George Carlin as some of his influences. When he was 10, his parents divorced. C.K. said that his Father was around but he did not see him much and when he remarried, C.K.'s Father converted to Orthodox Judaism, the faith of his new wife. C.K. and his three sisters were raised by their single mother in Newton, Massachusetts. The fact that his mother had only "bad" TV shows to view upon returning home from work inspired him to work on television. C.K.'s mother raised her children as Catholic and they attended after-school Catholic class until they completed communion. C.K. has said that his father's whole family still lives in Mexico. C.K.'s paternal uncle Dr. Francisco Székely is an academic and an international consultant on environmental affairs who served as Mexico's Deputy Minister of Environment (2000–2003).

C.K. innovated direct-to-consumer distribution in 2001 when he released his debut comedy album, Live in Houston, directly through his website. He became one of the first performers to use his website to offer direct-to-fan ticket sales to his stand-up shows, as well as DRM-free video concert downloads. In this way, C.K. sold tickets for his stand-up tour, circumventing large ticket outlets (e.g., Ticketmaster) by bypassing their overhead and the venues they control. C.K. has said the ticket outlets create barriers to consumers, whereas direct distribution is easy—and has effectively "closed the gap between how easy it was to steal it [versus] how easy it was to buy it". The success of the special prompted other comedians, including Jim Gaffigan, Joe Rogan, and Aziz Ansari, to release their own specials with a similar Business model.

C.K. appeared several times on Dr. Katz, Professional Therapist, and was a frequent guest on The Opie & Anthony Show radio show, which also featured his Lucky Louie co-star Jim Norton. C.K. was also a part of Opie and Anthony's Traveling Virus Comedy Tour with other comedians in 2007. In 2007, he hosted a three-hour phone-in show on the Service at the request of Opie & Anthony, during which he advised callers on their relationship troubles. During an interview with Secretary of Defense Donald Rumsfeld on the show, C.K. repeatedly asked Rumsfeld whether he is in fact a reptilian space alien who "eats Mexican babies". Rumsfeld declined to comment and the video has since gone viral. In the Louie episode "Barney / Never", Opie, Anthony, and Norton (along with Comedian Amy Schumer) play the on-air talent of a stereotypical wacky morning radio program into which C.K.'s character is calling to promote a gig in Kansas City.

C.K. and his wife Alix Bailey divorced in 2008, with C.K. and Bailey sharing joint custody of their children. In a 2010 interview, C.K. talked about how, after his divorce, he thought, "well, there goes my act." He alluded to the way that his marriage had been central to his act and his life, and he said that it took him approximately a year to realize "I'm accumulating stories here that are worth telling." One element in his preparation for stand-up was training at the same boxing gym as Lowell, Massachusetts fighter Micky Ward, trying to "learn how to ... do the grunt work and the boring, constant training so that you'll be fit enough to take the beating."

On April 18, 2009, C.K. recorded a concert film titled Hilarious. Unlike his previous specials—which had all been produced for television networks—Hilarious was produced independently, directed by C.K. himself, and sold to Epix and Comedy Central after it was complete. As a result, it was not released until late 2010. It was published on DVD and CD in 2011. It is the first stand-up comedy film accepted into the Sundance Film Festival. From 2009 to 2012, C.K. played Dave Sanderson, a police officer and ex-boyfriend of Leslie Knope (played by Amy Poehler) in the sitcom Parks and Recreation. He also co-starred in the romantic comedy fantasy film The Invention of Lying, directed by and starring Ricky Gervais, in 2009.

FX picked up C.K.'s series Louie in August 2009, which C.K. stars in, writes, directs, and edits. The show features stand-up routines blended with segments partially based on his offstage experiences which address his life as a divorced, aging Father. The show premiered on June 29, 2010. In season three, episodes dealt respectively with a date with an unstable bookshop clerk (played by Parker Posey); a doomed attempt to replace a retiring David Letterman; an aborted visit to C.K.'s father; and a dream-reality New Year's Eve episode in which C.K. ends up in China. These episodes were ranked in critic Matt Zoller Seitz's favorite 25 comedy episodes of 2012. Seitz called the episode "New Year's Eve" "truly audacious". C.K. has been nominated five times for the Primetime Emmy Award for Outstanding Lead Actor in a Comedy Series (2011–2015) for his work in Louie and won two Emmys in 2011 for the Louie episode "Pregnant" and for his special Live at the Beacon Theater.

In 2011, by selling Live at the Beacon Theater on his website, C.K. earned a "million dollars in matter of days, half of which he [gave] away to his staff and charities." Recipients included the Fistula Foundation, Green Chimneys, the Pablove Foundation, Charity: Water, and Kiva. In 2016, he selected the Fistula Foundation as the beneficiary of his Jeopardy! Power Players Week appearance, and won $50,000 for the charity.

C.K. hosted Saturday Night Live on November 3, 2012 and was subsequently Primetime Emmy Award-nominated for Outstanding Guest Actor in a Comedy Series. He returned to host the show on March 29, 2014 and May 16, 2015 and received Emmy nominations for Outstanding Guest Actor in a Comedy Series for both episodes. On April 8, 2017, he hosted Saturday Night Live for a fourth time. One of the sketches in which he appeared engendered controversy because of similarities to a short film by Actress and Comedian Tig Notaro, titled Clown Service. He executive produced the pilot for the Amazon Video black comedy series One Mississippi, starring Notaro, in November 2015. It was ordered for a full season by Amazon. Barry Crimmins's stand-up special, Whatever Threatens You, directed and produced by C.K., was released through his website in 2016.

The show was renewed for a fourth season; with a 19-month hiatus after season 3 to accommodate C.K.'s roles in David O. Russell's American Hustle and Woody Allen's Blue Jasmine in 2013. During the 2014 Television Critics Association presentations, FX Networks' John Landgraf reported that Louie would return in spring 2015 for a shortened fifth season of seven episodes—compared to the 13 episodes of prior seasons. The fifth season premiered in April 2015 and an announcement said the series would take an "extended hiatus" in August 2015; C.K. stated in January 2016 that he "just doesn't know" whether it will return or not. However, FX ended their Business partnership with Louis C.K in November 2017 after he confirmed that a series of sexual misconduct allegations against him were true, meaning the show would have to be picked up by another network.

In May 2015, it was announced that C.K. would write, direct, and star in the film I'm a Cop, to be produced by Scott Rudin, Dave Becky, and Blair Breard, with a budget of $8 million, although he later canceled the project. C.K. became the first Comedian to sell out Madison Square Garden three times in a single tour in 2015. Audio from the tour was released by C.K. on his website as Louis C.K.: Live at Madison Square Garden through the pay what you want model. In November 2015, C.K co-starred in the biographical drama film Trumbo as a composite character based on five different screenwriters who were blacklisted in Hollywood for their alleged ties to the Communist party during the 1940s.

In March 2016, C.K. sent an email to those subscribed to his mailing list with his opinion about the 2016 presidential race. He said he wanted a conservative President but criticized Republican Party presidential candidate Donald Trump as being like Adolf Hitler. He said Trump is an "insane bigot" even though he has captivating qualities. C.K. added, "He's not a Monster. He's a sad man." C.K. later referred to the e-mail as "irrational" and claimed he should never write his opinions again.

On November 9, 2017, the distributor of I Love You, Daddy, The Orchard, canceled the New York premiere of the film due to "unexpected circumstances". The Hollywood Reporter revealed that C.K.'s scheduled next-day appearance on The Late Show with Stephen Colbert had also been canceled and predicted that this was due to an upcoming New York Times story. The report, published later that day, revealed sexual harassment allegations by five women against C.K. One of the allegations described a 2005 encounter in which C.K. asked Comedian Rebecca Corry for permission to accompany her to a dressing room so that he could masturbate in front of her. The incident, which took place on the set of a television pilot, was reported to executive producers Courteney Cox and David Arquette who considered shutting down the production until Corry convinced them to continue. According to the comedy duo Dana Min Goodman and Julia Wolov, who detailed a visit to C.K.'s hotel room in 2002, C.K. made a similar request to them and proceeded to ejaculate on his stomach before receiving an answer. Goodman and Wolov recalled laughing at what they thought was a joke before being left speechless. One of their managers, Lee Kernis, named Dave Becky in this accusation for giving a hostile response. Becky, who manages prominent comedians such as Kevin Hart, Aziz Ansari and Amy Poehler has since apologized and dropped C.K. as a client. The account of an unnamed coworker on The Chris Rock Show, saying that she eventually assented to Louis C.K.'s pressure to watch him masturbate, was also included in the piece. These stories were corroborated by Comedian Abby Schachner who stated that Louis C.K. complimented her appearance and then audibly started to masturbate during a 2003 phone call. Corry and Schachner both added that they had received apologies in some form after several years.