Michael Shannon had been the front runner for the role, but the studio and Marvel have opted for the "Sicario" star, who has appeared in the Marvel Cinematic Universe as the villain Thanos, reported Variety.
Taking to Twitter, Reynolds also confirmed the casting of Brolin in a humorous post.
"Fox! You can't play 2 characters in the same universe!! Josh Brolin was in Sicario and I was in Sabrina The Teenage Witch," he wrote.
Reynolds is reprising his role as the wisecracking mercenary, with the story expanding to include other characters from Deadpool's corner of Marvel's X-Men universe.