In 1983, Winfrey relocated to Chicago to host WLS-TV's low-rated half-hour morning talk-show, AM Chicago. The first episode aired on January 2, 1984. Within months after Winfrey took over, the show went from last place in the ratings to overtaking Donahue as the highest rated talk show in Chicago. It was renamed The Oprah Winfrey Show, expanded to a full hour, and broadcast nationally beginning September 8, 1986.[33] On her 20th anniversary show, Oprah revealed that movie critic Roger Ebert was the one who persuaded her to sign a syndication deal with King World. Ebert predicted that she would generate 40 times as much revenue as his television show, At the Movies.[34] Already having surpassed Donahue in the local market, Winfrey's syndicated show quickly doubled his national audience, displacing Donahue as the number one day-time talk show in America. Their much publicized contest was the subject of enormous scrutiny.

Oprah.com is the premier online women's resource for everything Oprah. It provides people with the personal and lifestyle resources to live their best lives. Beginning with daily coverage of The Oprah Winfrey Show, Oprah.com provides millions of Internet users with extensive expert advice, interactive workbooks, photos, video, inspirational stories, books and product information from the show. Users can purchase tapes and transcripts from the show, email their own stories and ideas for show consideration, send in comments on recently aired programs, or post remarks on different message boards. From a complete review of Oprah's Favorite Things to step-by-step guides on cooking, entertaining, home decorating, fitness and health, Oprah.com creates a huge library of resources for viewers around the world. Video highlights from Oprah After the Show, aired on the Oxygen Network, can also be viewed exclusively on Oprah.com.

With more than 900,000 online members since its June 2003 launch, Oprah's Book Club has quickly become the largest book club in the world. Enrollment is free and provides members with access to benefits such as specialized reading guides for each book selection and Q&A sessions with literary experts. Book Club members can connect with other readers from their local area or create book clubs online with people from around the world.

In November 2003, an online adaptation of Oprah's hugely popular "Live Your Best Life" tour was launched on Oprah.com. A groundbreaking multimedia workshop taught by Oprah, the program allows users to personally share in the life moments that have helped Oprah live her best life and work through an extensive, Oprah-guided personal workbook to experience their own path toward greatness.

Oprah.com averages 64 million page views and more than three million unique visitors per month and receives an average of 12,000-15,000 e-mails each week.

During a lawsuit against Winfrey (see Influence), she hired Dr. Phil McGraw's company Courtroom Sciences, Inc. to help her analyze and read the jury. Dr. Phil made such an impression on Winfrey that she invited him to appear on her show. He accepted the invitation and was a resounding success. McGraw appeared on The Oprah Winfrey Show for several years before launching his own show, Dr. Phil, in 2002, which was created by Winfrey's production company, Harpo Productions, in partnership with Paramount which produced the show.

In 1985, Winfrey co-starred in Steven Spielberg's epic film adaptation of Alice Walker's Pulitzer Prize-winning novel The Color Purple. She earned immediate acclaim as Sofia, the distraught housewife. The following year Winfrey was nominated for an Academy Award for Best Supporting Actress, but she lost to Anjelica Huston. The Color Purple has now been made into a Broadway musical and opened late 2005, with Winfrey credited as a producer.