Manuel was replaced by Hall of Famer and former Cubs second baseman Ryne Sandberg, the Phillies ' third-base coach. Sandberg managed the Phillies ' Triple-A team at Lehigh Valley the previous two seasons.
The team said Sandberg will take over beginning with Friday night's game against the first-place Los Angeles Dodgers. He was introduced at a news conference before the game.
The Phillies have lost 19 of 24 since last month's All-Star break. They are in fourth place and 20½ games out of first in the NL East.
The 69-year-old Manuel has been a folksy presence in the Phillies ' dugout since the beginning of the 2005 season. He led Philadelphia to a World Series title in 2008 and brought the team back to the series in 2009, when they lost to the Yankees.
Manuel was 780-636 with the Phillies and won five straight NL East titles from 2007-2011. He also spent three years as manager with the Cleveland Indians, winning the AL Central in 2001.
Even with an aging roster, the Phillies were expected to contend in the NL East this season, but the team has fallen apart.
Two-time Cy Young Award winner Roy Halladay has missed most of the season with an injury. Slugger Ryan Howard also has been out with an injury. High-priced reliever Jonathan Papelbon has struggled to close, and apart from Chase Utley and Dominic Brown the Phillies haven't hit much.