Volokh was born in Kiev, Ukraine, then part of the Soviet Union. He emigrated with his family to the United States at age seven. At age 12, he began working as a computer programmer; three years later, he received a Bachelor of Science degree in Math and Computer Science from UCLA. During this period, his achievements were featured in an episode of OMNI: The New Frontier, a television series hosted by Peter Ustinov. In 1992, Volokh received a Juris Doctor degree from the UCLA School of Law. He was a law clerk for Judge Alex Kozinski of the Ninth Circuit Court of Appeals and later for Justice Sandra Day O'Connor of the U.S. Supreme Court. Since finishing his clerkship, he has been on the faculty for the UCLA School of Law.

Eugene Volokh is married and has two children. His mother, Anne Volokh, founded Movieline magazine in 1985. His father, Vladimir Volokh, is a software engineer. His brother, Alexander "Sasha" Volokh, a law professor at Emory Law School, is a co-blogger at the Volokh Conspiracy.

Volokh is a libertarian-leaning conservative. He is noted for his scholarship on the First and Second Amendments to the United States Constitution, as well as on copyright law. His article, " The Commonplace Second Amendment" was cited by Supreme Court Justice Antonin Scalia's majority opinion in the landmark Second Amendment case of District of Columbia v. Heller (128 S. Ct. 2783, 2789). He advocates campus speech rights and religious freedom, and opposes racial preferences, having worked as a legal advisor to California's Proposition 209 campaign. He is a critic of what he sees as the overly broad operation of American workplace harassment laws, including those relating to sexual harassment.

On his weblog, Volokh addresses a wide variety of issues, with a focus on politics and law. He has criticized student law review article citations of Wikipedia, arguing that information found on Wikipedia may be unreliable.

Volokh's non-academic work has been published in The Wall Street Journal, Los Angeles Times, The New York Times, Slate, and other publications. Since May 2005 he has been a contributing blogger at The Huffington Post.