Mlodinow was born in Chicago, Illinois, of parents who were both Holocaust survivors. His father, who spent more than a year in the Buchenwald death camp, had been a leader in the Jewish resistance under Nazi rule in his hometown of Czêstochowa, Poland. As a child, Mlodinow was interested in both mathematics and chemistry, and while in high school was tutored in organic chemistry by a professor from the University of Illinois.

As recounted in his book, Feynman's Rainbow, his interest turned to physics during a semester he took off from college to spend on a kibbutz in Israel, during which he had little to do at night beside reading The Feynman Lectures on Physics, which was one of the few English books he found in the kibbutz library.

While a doctoral student at the University of California, Berkeley, and on the faculty at Caltech, he developed (with N. Papanicolaou) a new type of perturbation theory for eigenvalue problems in quantum mechanics. Later, as an Alexander von Humboldt fellow at the Max Planck Institute for Physics and Astrophysik in Munich, Germany, he did pioneering work (with M. Hillery) on the quantum theory of dielectric media.

Apart from his research and books on popular science, he also wrote the screenplay for the film Beyond the Horizon and has been a screenwriter for television series, including Star Trek: The Next Generation and MacGyver. He co-authored (with Matt Costello) a children's chapter book series entitled The Kids of Einstein Elementary.

Mlodinow currently teaches at Caltech and has completed a new book with Stephen Hawking entitled, The Grand Design. A step beyond Hawking's other titles, The Grand Design explores both the question of the existence of the universe and the issue of why the laws of physics are what they are.

Euclid's Window - The Story of Geometry from Parallel Lines to Hyperspace is a work on popular science that chronicles the idea of curved space and the history of geometry. It proved a popular success and has now been translated into ten languages. Feynman's Rainbow: a Search for Beauty in Physics and in Life - Is a story about Mlodinow's relationship with Richard Feynman, during his post-doctoral years in Caltech, in the early eighties. The book offers an insight into Feynman's attitude towards physics and life, his relationship with Murray Gell-Mann and the rise of String Theory. A Briefer History of Time - Co-authored with Stephen Hawking, this book became an international best-seller that has appeared in 25 languages. The Drunkard's Walk: How Randomness Rules our Lives - This work deals with randomness and people's inability to take it into account in their daily lives. The book was a bestseller, and a "NY Times notable book of the year" and was named "one of the 10 best science books of 2008" on Amazon.com.