Dawkins had 37 interceptions and 26 sacks in 13 seasons with the Eagles and the past three with the Broncos. The 1996 second-round pick also played in a Super Bowl for Philadelphia.
"The Lord has blessed me to play in the NFL for 16 years," Dawkins, 38, said on his Twitter account. "I would like to thank the Eagles & the Broncos 4 believing in me.
"I am announcing my retirement from the NFL."
Dawkins battled neck injuries toward the end of the 2011 NFL season and missed two of the Broncos' final three games of the regular season and their two playoff games.
Both of his former teams praised Dawkins for his commitment to the game.
"Brian Dawkins is one of the best to ever play the game, a future Hall of Famer who changed the way his position is played," Broncos head coach John Fox said in a statement.
"On the field, in many ways, Brian re-invented the safety position. He had the speed and athleticism to line up against the game's best receivers, and was equally effective in the run game," Eagles owner Jeffrey Lurie said in a statement.
"His love for the game was infectious and he poured his entire heart and soul into everything he was doing from the moment he entered the stadium until he left."