Tatopoulos was born and raised in Paris, France, to an immigrant father from Macedonia, Greece, and a French mother. His parents had a clothing store in Paris. Patrick Tatopoulos raced motorcycles, worked in 2-D advertising and drew comic book covers. He lived in Greece for ten years before coming to the United States in 1989. He is tri-lingual, a fluent speaker of French, Greek and English.

In May 2000, Tatopoulos was honored by The Hellenic Times at its ninth annual Scholarship Gala in New York. The goal of the organization is to identify young American scholars who best exemplify the values of their Greek heritage and provide them with educational support. A Patrick Tatopoulos Creative Arts Award Scholarship was created in 2001 and Tatopoulos has personally presented the scholarship, in his name, to a deserving student in 2001 and 2002. He owns Tatopoulos Studios, Inc. and Patrick Tatopoulos Designs, Inc.

The character of Niko Tatopoulos in Godzilla was named after his youngest daughter. He made his directorial debut with the 2009 film, Underworld: Rise of the Lycans. He worked on the live action film adaptation of the Darkstorm Studios graphic novel I, Frankenstein, which was produced by Lakeshore Entertainment. The story follows the original Monster of Victor Frankenstein who is the only force that stands between the human race and an uprising of supernatural creatures determined to overthrow the world. Filming kicked off in July 2010. The film was released in 2014. Tatopoulos created the creature figures of the upcoming Stan Winston produced Speed Demon. He will direct the action horror film Suspension, which based on a screenbook by Scott Millam.

On October 11, 2015, Tatopoulos married Face Off host McKenzie Westmore. The couple met while working on the first season of the show. The wedding ceremony was held at Chateau Le Dome at Saddlerock Ranch Winery in Malibu, California. Tatopoulos is currently living in Los Angeles.