Tarbell was born in Erie County, Pennsylvania, the daughter of Pennsylvania Republicanss. Two of her brothers knew Abraham Lincoln, and her father was forced out of business by John D. Rockefeller's Southern Improvement Company, a predecessor to Standard Oil. These connections would prove influential in her later career. She received her bachelor's degree in 1880 and her master's in 1883, both from Allegheny College.
She was hired by McClure's magazine in 1894, and her series on Abraham Lincoln nearly doubled the magazine's circulation. She soon turned to investigative journalism, and she and her fellow staff members Ray Stannard Baker and Lincoln Steffens became a celebrated muckraking trio. Her investigations of Standard Oil for McClure's, which ran in 19 parts from November 1902 to October 1904, were collected and published as The History of the Standard Oil Company in 1904. It placed fifth in a 1999 list of the top 100 works of journalism in the 20th century.
Although public opposition to Rockefeller and Standard Oil existed prior to Tarbell's investigation, it fueled public attacks on Standard Oil and in trusts in general, and the book is credited with hastening the 1911 breakup of Standard Oil. "They had never played fair, and that ruined their greatness for me," she wrote about the company.
In 1906, Tarbell, Baker, Steffens, and editor John Phillips left McClure's and bought American Magazine, where they departed from the muckraking style and adopted a more optimistic approach. She and most of the rest of the staff left the magazine in 1915. During this time, Tarbell also contributed to Collier's Weekly.
Tarbell's other books included Life of Abraham Lincoln (1900), The Business of Being a Woman (1912), The Ways of Women (1915), biographies of Elbert H. Gary (1925) and Owen D. Young (1932), The Nationalizing of Business, 1878-1898 (1936), and her autobiography, All in the Day's Work (1939).
She died of pneumonia in 1944, at the age of 86.
On October 7, 2000, Tarbell was inducted into the National Women's Hall of Fame in Seneca Falls, New York. On September 14, 2002, the United States Postal Service issued a commemorative stamp honoring Tarbell as part of a series of four stamps honoring women journalists.