Spike TV's Video Game Awards will celebrate its 10th Anniversary when it airs live in over 100 countries and territories around the world on Friday, December 7 at 9pm ET.
The Avengers star previously hosted the awards show three times from 2005 to 2007.
"I'm thrilled to once again preside over the biggest night of gaming," Jackson said in a statement.
Mark Burnett, who will serve as an executive producer of the televised event, also shared: "I'm a huge Samuel L Jackson fan and literally can't get enough of him. What an amazing opportunity to work with Spike for the second time and with him for the first time."
Jackson will follow his hosting stint with Quentin Tarantino's Django Unchained, which opens to cinemas on December 25, 2012 in the US and January 18, 2013 in the UK.
Watch a video featurette of The Avengers below: