After his first films proved to be box-office flops, Zemeckis directed Romancing the Stone starring Michael Douglas. The film was a big success, and Zemeckis went on to direct the Back to the Future trilogy of films. These films established him as a leading director in Hollywood.

He is known for his innovative use of special effects, especially in Who Framed Roger Rabbit, which combined live action seamlessly with traditional animation, and Forrest Gump, in which he placed Tom Hanks in scenes with well-known historical figures such as John F. Kennedy. His most recent project, 2004's The Polar Express, based on the children's book by Chris Van Allsburg, utilized the computer animation technique known as performance capture, whereby the movements of the actors are captured digitally and used as the basis for the animated characters.

Since becoming a well-known Hollywood director, he has been nominated for and won several awards, including the Academy Award for Directing for Oscar-nominated Forrest Gump in 1994. In 1999, Zemeckis donated $5 million towards the Robert Zemeckis Center for Digital Arts at USC, which today hosts many film school classes, much of the Interactive Media Division, and Trojan Vision, USC's student television station which has won 4 Tellys and has been voted the number one college television station in the country.

He often works with composer Alan Silvestri and writer Bob Gale.