Pulliam was born in a sod dugout house in Ulysses, Kansas, the son of the Reverend Irvin Brown and Martha Ellen (Collins) Pulliam, Methodist missionaries sent to plant churches in the frontier towns of western Kansas. The Pulliams moved frequently and young Eugene grew up in a variety of dusty prairie towns. Pulliam got his first taste of the newspaper business as a six-year-old paperboy selling papers to Missouri Pacific Railroad passengers at the railroad station in Chanute, Kansas.
In 1907, Pulliam entered DePauw University in Indiana. At DePauw, Pulliam was a member of Delta Kappa Epsilon fraternity (Psi Phi chapter) and founded the DePauw Daily, a student newspaper. He also helped found Sigma Delta Chi.
Pulliam dropped out of college after his junior year and moved to Atchison, Kansas where he got a job at the Atchison Champion. A few months later, he received a job offer from The Kansas City Star, then the largest newspaper in the lower Midwest. He moved to Kansas City and became a reporter.
In 1911, aged 23, he became one of the youngest newspaper editors in the nation when he took over operation of the Atchison Champion. A year later he married Myrta Smith, a former college classmate. With financial backing from her family, he purchased the Atchison Champion, the first of 46 newspapers he would come to own.
After giving birth to a son, Eugene S. Pulliam, Myrta died in 1917. In 1919, Eugene married Martha Ott and fathered two more children, Corinne and Suzanne. Eugene and Martha divorced in 1941. Later in 1941 he married his third and last wife, Nina Mason.
Pulliam's publishing empire came to include the Franklin (Indiana) Evening Star, the The Lebanon Reporter, The Indianapolis Star, the Muncie Star, the Arizona Republic and its one-time rival the Phoenix Gazette, the Indianapolis News, and the Huntington Herald-Press. He also owned several radio stations including WIRE radio in Indiana and KTAR in Arizona.
In 1934, Pulliam consolidated his holdings into Central Newspapers, Inc., a holding company designed to streamline the operations of his far flung assets. Central Newspapers continued to grow until it became a billion dollar media conglomerate owning outlets in Indiana, Arizona, Georgia, Oklahoma, Kentucky, North Carolina, New Jersey, Pennsylvania, and Massachusetts.
Son Eugene S. Pulliam joined the family business in 1935 as director of WIRE. Son-in-law James C. Quayle joined the business and headed several newspapers, including the Arizona Republic. Grandson Dan Quayle, the future Vice President of the United States, began his career at the Huntington Herald-Press.
Pulliam was for the most part a noted conservative and an active supporter of the Republican Party, although he endorsed Lyndon Johnson over Barry Goldwater in the 1964 presidential race. He was an outspoken advocate of freedom of the press.
Eugene C. Pulliam died at his home in Arizona in 1975, aged 86. His widow, Nina Mason Pulliam, took over the presidency of Central Newspapers, holding the office until 1979. She also became the publisher of the Arizona Republic and the Phoenix Gazette. His son Eugene S. Pulliam took over as publisher of the Indianapolis Star and the Indianapolis News. His granddaughter Myrta Pulliam contributed to the Indianapolis Star's 1974 Pulitzer Prize-winning stories on police corruption.
On August 1, 2000 Central Newspapers, Inc. was acquired by the Gannett Company, Inc., for $2.6 billion. His estate, the Eugene C. Pulliam Trust, owned 78% of the company's stock and was the principal beneficiary of the transaction.
As a condition of his will, Pulliam ordered that the trust could not sell the corporation unless it was "seriously threatened" by a "substantially complete loss" of value. In a somewhat controversial move the trustees interpreted this clause loosely and declared that the merger would be the only way to prevent the corporation from suffering a long term loss of value.