Shelton and Harmon become the fourth and fifth members of the Patriots to join the Lions over the past two offseasons under Detroit head coach Matt Patricia, the former Patriots defensive coordinator.
Shelton was one of the surprise stories of the Patriots' 2019 season after re-signing with the team on a modest one-year deal in late May, well after the initial free-agent flurry.
At the time, he was projected to be on the roster bubble. Instead, he emerged as a starter alongside Lawrence Guy as the Patriots' second big-bodied defensive tackle. Shelton played in all 16 regular-season games, setting career highs with 61 tackles and three sacks.
His primary role came on early downs, and he would often be replaced in more obvious passing situations. At 6-foot-2 and 345 pounds, Shelton plays with great strength, which is one of his primary assets.
Shelton, 26, entered the NFL as a 2015 first-round draft choice of the Cleveland Browns. The Patriots initially acquired him in a trade on March 15, 2018, and he was a solid fit in their multiple schemes.
Terms of the Harmon trade, which was first reported by NFL Network, were not immediate available.
Harmon, 29, has been a consistent player for the Patriots over the first seven years of his career, playing 111 of 112 possible games with 29 starts with 175 tackles and 17 interceptions along with 28 passes defended.
He will likely fit in with Detroit in its three safety looks, potentially as a replacement for Tavon Wilson, who is slated to officially become a free agent later Wednesday.
ESPN's Mike Reiss and Michael Rothstein contributed to this report.