White was born in Mount Vernon, New York and graduated from Cornell University (his nickname "Andy" derives from Cornell cofounder Andrew Dickson White). He spent several years working as a newspaper writer and ad man before returning to New York City in 1924.
He published his first article in the newly founded The New Yorker magazine in 1925, then joined the staff in 1927. This made his fame for the next few decades, as he produced a long series of essays for them that were widely read as the magazine grew in influence. Over time he became the most important contributor to The New Yorker at a time when it was arguably the most important American literary magazine. He also served as a columnist for Harper's Magazine from 1938 to 1943.
In the late 1930s he turned his hand to children's fiction on behalf of a niece. His first children's book Stuart Little was published in 1945, and Charlotte's Web appeared in 1952. Both were highly acclaimed, and in 1970 jointly won the Laura Ingalls Wilder Medal, a major prize in the field of children's literature. In the same year, he published his third children's novel, The Trumpet of the Swan.
In 1959 he edited and updated the classic The Elements of Style. Originally written and published in 1918 by William Strunk Jr, the book is a handbook of grammatical and stylistic dos and don'ts for written American English. White had studied under Strunk while at Cornell in the years following World War I. Further editions of the work followed in 1972, 1979, and 2000. It is a standard accessory for students and writers.
In 1978 he was awarded a special Pulitzer Prize for his work as a whole. Other awards he received included a Presidential Medal of Freedom in 1963, and memberships in a variety of literary societies throughout the United States.
White married Katharine Sergeant Angell in 1929, also an editor at the magazine and author (as Katharine White) of Onward and Upward in the Garden. They had a son, Joel, a boatbuilder. Katharine's son from her first marriage, Roger Angell, was a fiction editor for the New Yorker, but is perhaps better known as a baseball writer.
White's style was stereotypically "Yankee": wry, understated, thoughtful, and informed. He was widely regarded as a master of the English language as writer's tool, noted for clear, well-constructed, and charming prose.