CBS Sports Digital is the second-largest sports property in the US, with a number of platforms, including SportsLine, CBSSports.com, CBS Sports Fantasy, CBS Sports apps and 247Sports.
William Hill will benefit from exclusive rights for brand promotion across all platforms.
The operator’s data, odds and markets will also be featured across CBS television programming.
The partnership will begin with initial integrations in March, with a full rollout planned for the fantasy football season.
Joe Asher, CEO of William Hill US, said: "CBS Sports, similar to William Hill, has a longstanding history of connecting fans directly to the biggest events and most iconic moments in sports.
"We are excited about this partnership, with assets including mass-reach digital content products, one of the largest fantasy sports databases and platforms in the world and leading sports television programming, which will allow us to expand the William Hill brand across America quickly and efficiently."
Jeffrey Gerttula, EVP and General Manager of CBS Sports Digital, said: "We’re thrilled to launch this momentous partnership, which allows us to deepen our investment and further extend our leadership in delivering multi-platform sports wagering content, while providing William Hill with unprecedented reach for its market-leading betting platform as it continues to grow its US business."