Around 1990, Perry moved to Atlanta, where two years later I Know I’ve Been Changed was first performed at a community theater, financed by the 22-year-old Perry’s $12,000 life savings. The play included Christian themes of forgiveness, dignity, and self-worth, while addressing issues such as child abuse and dysfunctional families. The musical initially received a “less than stellar” reception and was a financial failure. Perry persisted, and over the next six years he rewrote the musical repeatedly, though lackluster reviews continued. In 1998, at age 28, he succeeded in retooling the play and restaging it in Atlanta, first at the House of Blues, then at the Fox Theatre. Perry continued to create new stage productions, touring with them on the so-called “Chitlin’ Circuit” (now also known as the “urban theater circuit”) and developing a large, devoted following among African-American audiences. In 2005, Forbes reported that he had sold “more than $100 million in tickets, $30 million in videos of his shows and an estimated $20 million in merchandise”, and “the 300 live shows he produces each year are attended by an average of 35,000 people a week”.

Perry’s first book, Don’t Make a Black Woman Take Off Her Earrings: Madea’s Uninhibited Commentaries on Love and Life, appeared on April 11, 2006. The book sold 30,000 copies. The hardcover reached number one on the New York Times Best Seller list and remained on the list for 12 weeks. It was voted Book of the Year, Best Humor Book at the 2006 Quill Awards.

Despite praising Perry in 2006, director Spike Lee criticized his work in 2009, stating “Each artist should be allowed to pursue their artistic endeavors but I still think there is a lot of stuff out today that is ‘coonery buffoonery’.” When asked if Perry’s success among black audiences was a result of just giving black America what they wanted, Lee responded, “the imaging is troubling.”

Perry’s next Lionsgate project, Daddy’s Little Girls, starred Gabrielle Union and Idris Elba and was released in the United States on February 14, 2007. It grossed over US$31 million. Perry wrote, directed, produced and starred in his next film, Why Did I Get Married?, released on October 12, 2007. It opened at number one, grossing US$21.4 million that weekend. It is loosely based on his play of the same name. Filming began March 5, 2007, in Whistler, British Columbia, a resort town north of Vancouver, then moved to Atlanta, where Perry had opened his own studio. Janet Jackson, Sharon Leal, Jill Scott, and Tasha Smith appeared in the film. Perry’s 2008 film, Meet the Browns, released on March 21, opened at number 2 with a US$20.1 million weekend gross. The Family That Preys opened on September 12, 2008, and grossed over US$37.1 million.

Perry produced the long-running sitcom Tyler Perry’s House of Payne, which ran for 8 seasons from June 21, 2006, to August 10, 2012. The series followed an African-American household of three generations. The show demonstrated the family members’ serious, true-to-life struggles with faith and love. The show ran in the spring of 2006 as a 10-show pilot. After the successful pilot run, Perry signed a US$200 million, 100-episode deal with TBS. On June 6, 2007, the first two episodes of Tyler Perry’s House of Payne ran on TBS. After receiving high ratings, House of Payne entered broadcast syndication. Reruns were played through December 2007 before the second season began. Perry also wrote, directed and produced the sitcom Meet the Browns, which premiered on TBS on January 7, 2009 and ended on November 18, 2011.

In 2007, Perry bought a 17-acre estate in the Paces neighborhood of Buckhead, Atlanta. In May 2016, he sold the house for $17.5 million, also closing the biggest deal ever for a private home in the Georgia capital. In 2013, his company, ETPC LLC, purchased around 1,100 acres (4.5 km) in the New Manchester, Georgia area of Douglas County, Georgia.

Perry released his thirteenth film, Temptation: Confessions of a Marriage Counselor (based on his 2008 play of the same name) on March 29, 2013. The film stars Lance Gross, Jurnee Smollett, Brandy Norwood, Robbie Jones, Vanessa L. Williams, and Kim Kardashian. He produced Tyler Perry Presents Peeples, released on May 10, 2013. He returned to the big screen with A Madea Christmas, released on December 13, 2013. Perry directed the film The Single Moms Club, which opened on March 14, 2014. His first animated movie Madea’s Tough Love was released on DVD January 20, 2015. In 2016, Perry played scientist Baxter Stockman in Teenage Mutant Ninja Turtles: Out of the Shadows. In mid January 2016, Perry started filming his seventeenth film, and ninth within the Madea franchise, Boo! A Madea Halloween. The film was released on October 21, 2016. A sequel, Boo 2! A Madea Halloween, was released in October 2017. Perry, alongside Oprah Winfrey, lent his voice in his first computer-animated film, called The Star, which is based on the Nativity of Jesus. Developed by Sony Pictures Animation, the film was released on November 17, 2017.

The Writers Guild of America, West filed unfair labor practice charges with the National Labor Relations Board (NLRB), alleging that Perry’s production company, Tyler Perry Studios, unlawfully fired four writers in October 2008 in retaliation for them trying to get a union contract. The dispute was settled a month later, when Tyler Perry Studios agreed to be a WGA signatory.

Madea Goes to Jail opened at number one on February 20, 2009, grossing US$41 million and becoming his largest opening to date. This was Perry’s seventh film with Lionsgate Entertainment. At the request of director J. J. Abrams, also in 2009, Perry had a small role as the Starfleet Academy commandant Admiral Barnett in Star Trek, which opened on May 8. This was his first film appearance outside of his own projects. Perry next wrote, directed, and starred in I Can Do Bad All By Myself (2009), a film structured around his Madea character. This was Perry’s eighth film and it also made number one at the box office. In 2009, Perry teamed with Oprah Winfrey to present Precious, a film based on the novel Push by Sapphire. Why Did I Get Married Too?, the sequel to Why Did I Get Married?, opened in theaters on April 2, 2010. It featured Janet Jackson, Cicely Tyson, Louis Gossett Jr., Jill Scott, and Malik Yoba. The film grossed US$60 million domestically, with US$29 million made the opening weekend.

In early 2009, Perry threatened legal action against Mo’ Money Taxes, a tax preparation company based in Memphis, Tennessee, for running a TV spot that he felt offensively parodied his work, in particular Madea Goes to Jail. The ad features a large Caucasian male (John Cowan) in drag, named “Ma’Madea”. The offending ad was dropped from circulation.

In October 2009, during a 60 Minutes interview, Perry was read a quote of Spike Lee’s comments about his work and responded, “I would love to read that [criticism] to my fan base. … That pisses me off. It is so insulting. It’s attitudes like that that make Hollywood think that these people do not exist, and that is why there is no material speaking to them, speaking to us.” Perry also stated that “all these characters are bait – disarming, charming, make-you-laugh bait. I can slap Madea on something and talk about God, love, faith, forgiveness, family, any of those.” In an interview with Hip Hollywood, Perry responded to Spike Lee’s comments by telling him to “go to hell.”

On July 20, 2009, Perry sponsored 65 children from a Philadelphia day camp to visit Walt Disney World, after reading that a suburban swim club, the Valley Swim Club in Huntingdon Valley, Pennsylvania, had shunned them. He wrote on his website, “I want them to know that for every act of evil that a few people will throw at you, there are millions more who will do something kind for them.”

On December 8, 2009, Perry’s mother, Willie Maxine Perry, died at age 64, following an illness. As of 2020, he is unmarried. He lives and works in Southwest Atlanta where he operates the Tyler Perry film and TV studios. In August 2010, it was reported that he had purchased Dean Gardens, a 58-acre estate in the Atlanta suburb of Johns Creek. He tore down the existing 32,000-square-foot (3,000 m) mansion and planned, but never built, a new, environmentally-friendly home on the property.

Perry’s films are co-produced and distributed by Lions Gate Entertainment; he retains full copyright ownership under the corporate name Tyler Perry Films, and places his name in front of all titles. Perry’s movies have seen very limited release outside North America, but in May 2010, Lionsgate announced plans to begin releasing his films in the United Kingdom.

Perry directed a film adaptation of Ntozake Shange’s 1975 choreopoem For Colored Girls Who Have Considered Suicide When the Rainbow Is Enuf, which was released in theaters November 5, 2010. He appeared in the stage show Madea’s Big Happy Family, which toured the U.S. as a stage play and was released as a movie in 2011, written, directed by and starring Perry. The film version of Madea’s Big Happy Family raked in US$25.8 million at the box office, taking second place. Perry’s next film with Lionsgate was Good Deeds, in which Perry plays lead character Wesley Deeds. Good Deeds is a romantic drama film written, directed by, and starring Perry. The film was released on February 24, 2012. It is the tenth of eleven films that Perry directed and appears in. The film received a 29% rating by review aggregator Rotten Tomatoes and opened with a box office US$15.5 million gross. The movie also stars Thandie Newton, Rebecca Romijn, Gabrielle Union, Eddie Cibrian, Jamie Kennedy, Phylicia Rashad, and others.

Tyler Perry’s For Better or Worse, based on his films Why Did I Get Married? and Why Did I Get Married Too?, premiered on TBS on November 25, 2011. The series was cancelled by TBS in February 2013 but was revived by OWN for a third season, which began on September 18, 2013.

As of June 2011, Perry’s films had grossed over US$500 million worldwide. Perry’s Madea’s Witness Protection, his seventh film within the Madea franchise, was released on June 29, 2012.

Perry took over the role of James Patterson’s Alex Cross from Morgan Freeman for a new film in the series, titled Alex Cross. The film opened on October 19, 2012, and received praise from critics and audiences for his role. His performance gained the attention of director David Fincher, who subsequently cast Perry in his 2014 thriller Gone Girl, co-starring with Ben Affleck, Rosamund Pike, and Neil Patrick Harris.

On October 2, 2012, Perry struck an exclusive multi-year partnership with Oprah Winfrey and her Oprah Winfrey Network (OWN). The partnership was largely for the purposes of bringing scripted television to OWN, Perry having had previous success in this department.

Perry also has two other new television series featured on OWN: the hour-long soap opera/drama series The Haves and the Have Nots and the sitcom Love Thy Neighbor. The Haves and the Have Nots premiered on May 28, 2013, while Love Thy Neighbor premiered on May 29, 2013. It was reported on May 29, 2013 that The Haves and the Have Nots set a new record for OWN, scoring the highest ratings ever for a series premiere on the network. Love Thy Neighbor scored the second highest ratings ever for a series premiere on OWN, behind The Haves and the Have Nots; however, Love Thy Neighbor has significantly declined in ratings while The Have and the Have Nots has continued to increase its ratings. On February 4, 2014, The Haves and the Have Nots came in as the most watched program in all of cable television for the night. On Tuesday, March 11, 2014, a Haves and the Have Nots season 2 episode set an OWN record when it scored the highest ratings in the network’s history. The record-breaking episode brought in 3.6 million viewers, surpassing the 3.5 million that tuned in for the Oprah’s Next Chapter interview with Bobbi Kristina which was the network’s previous highest rated viewing.

On January 9, 2014, as part of Perry’s continued partnership with OWN, the network ordered its fourth scripted series (and fourth series by Perry) based on the feature film, The Single Moms Club, called If Loving You Is Wrong. The hour-long drama series premiered on September 9, 2014.

On November 30, 2014, Perry’s partner Gelila Bekele gave birth to their son.

In 2015, Perry acquired the 330-acre former military base Fort McPherson located in Atlanta, which he converted to studios. The studios were used to film the HBO Films/OWN film version of The Immortal Life of Henrietta Lacks, and is currently in ongoing use for the television series The Walking Dead. 50,000 square feet of the site are dedicated to standing permanent sets, including a replica of a luxury hotel lobby, a White House replica, a 16,000-square-foot mansion, a mock cheap hotel, a trailer park set, and a real 1950s-style diner that was relocated from a town 100 miles away; it also hosts 12 sound stages named after highly accomplished African-Americans in the entertainment industry. The blockbuster Marvel film, Black Panther, was the first to be filmed on one of the new stages at Tyler Perry Studios as announced personally by Tyler Perry on his Instagram account on February 19, 2018.

On June 14, 2017, Perry signed a long term deal with ViacomCBS for 90 episodes/year of original drama and comedy series. Viacom will also have distribution rights to short video content and a first look at film concepts (the first film from this deal was Nobody’s Fool). The TV deal began fall 2019 with The Oval, Sistas and BET+ (a brand new streaming service) premiering with strong ratings for BET.

His second book, Higher Is Waiting, was published on November 14, 2017. It debuted at number 5 on the New York Times Best Seller list.

In September 2017, Perry purchased a house in Mulholland Estates, a gated community in Los Angeles.

On January 6, 2020, Perry posted a video on Instagram in which he revealed that he doesn’t use a writers room for his films and TV shows and prefers to write his work himself. Perry received criticism from several outlets and figures in entertainment for denying opportunities to up-and-coming black writers. Later that month, Perry responded in an interview by stating that he had experienced issues when working with both WGA writers and nonunion writers. He claims that the WGA writers would submit “scripts that would need rewrites in order to get paid multiple times.” He also said that nonunion writers struggled to meet his standards of quality and that he “was unhappy with every single script they wrote” because “they were not speaking to the voice.”