The left-handed Charlton was best known as being part of the infamous "Nasty Boys" relief pitching corps for the 1990 Reds team who won the World Series.Randy Myers and Rob Dibble were the other two members. The Boys were renowned for their clutch, shutdown performances, particularly during the playoff run; their blazing fastballs; and their bruising beanballs. Charlton is also famous in Cincinnati for plowing over Mike Scioscia to score a run in a nationally televised Sunday night game.
Charlton was also a key member of the two most beloved Mariner teams. During the 1995 "Refuse to Lose" team that was the first Mariner team to reach the playoffs, he was the team's closer after a midseason trade. As a member of the 2001 team that won an MLB record 116 games, he was a lefty specialist, fleshing out a bullpen which also featured Japanese closer Kazuhiro Sasaki, Jeff Nelson, and fellow lefty Arthur Rhodes.
Before the 1998 season, Charlton signed a contract to join the Baltimore Orioles bullpen. His subsequent poor pitching however led to an explosion of his ERA to 6.94. Baltimore was expected to contend in 1998 after having made the playoffs in 1997, but Charlton's lackluster performance was a factor in the Orioles having a losing record. Charlton was released on July 28. He signed with the Braves a few days later.
On October 22, 2007, the Mariners named him their bullpen coach. Charlton's contract, along with those of the remainder of the 2008 coaching staff, was not renewed following the hire of Don Wakamatsu as the club's field manager in November 2008.