Walker, who also presents BBC Breakfast and The NFL Show, joined the corporation’s flagship football magazine show in 2009 but will step down at the end of the current season.
He will remain with the company and will continue to work within BBC Sport, including at this summer’s Tokyo Olympics.
He also hinted at pursuing “further exciting opportunities”.
“It has been an amazing 12 years and I have loved every second of it,” he said in a statement released on social media. “I am so proud of the job we’ve done, the changes we’ve made and issues we’ve looked at while the football landscape changed immeasurably.
“I’d like to say thank you to the amazing team at Focus who put so much into the show each week and thank you to the audience for tuning in every Saturday.”
Head of TV at BBC Sport Philip Bernie expressed his gratitude for Walker’s efforts over more than a decade.
“Dan has been exceptional as presenter of Football Focus for the last 12 years,” he said.
“He is a top-class broadcaster who has brought authority, wit and fun to the show, always working so well with such warmth with the guests on the show.
“We are extremely grateful for all he given to Focus, and will continue to enjoy watching him on the BBC’s sport output as well as the wider BBC.”