Henne decided to have shoulder surgery and was placed on the injured reserve list Thursday.
The Dolphins replaced him on the roster by signing veteran quarterback Sage Rosenfels, who was released Tuesday by the New York Giants after recovering from a blood disorder that sent him to the hospital in August.
Henne separated his left shoulder when tackled on a busted play in the first quarter of Sunday's loss at San Diego. The game might have been Henne's last with Miami, because his contract expires after the season.
"It's really disappointing," coach Tony Sparano said. "The kid's got a lot invested in this thing with the team."
Henne lost his past seven starts for the Dolphins, who are 0-4 with a bye this week. Immediately after the game, he expressed optimism he would quickly be back in the lineup, but the injury turned out to be more serious than he anticipated.
"It's tough," teammate Jake Long said. "Chad's one of those guys, he's like me, he'll do anything he can to get out on the field. But he can't."
Moore took 150 snaps during three days of practice this week. The only other healthy QB with the team was rookie Pat Devlin, a member of the practice squad.
"It's Matt's job. We've got to get Matt ready to go," Sparano said. "He's a confident guy -- a little different swagger to him when he gets in the huddle."
Moore will become the 16th quarterback to start for the Dolphins since Dan Marino retired following the 1999 season. The list include Rosenfels, who started one game in 2004 and another in 2005. He also started 10 games for Houston in 2007-08.
Now 33, Rosenfels had a strong preseason for the Giants before becoming ill. He was one of several free-agent quarterbacks the Dolphins tried out this week.
"Sage is experienced," Sparano said. "He was a guy that was best in the workout."
Rosenfels hasn't thrown a pass in a regular-season game since 2008. He won't join practice until Tuesday, when the Dolphins return from a weekend break.
Moore is a fourth-year pro with 23 career starts, all with Carolina. Last year he went 1-4 as a starter before a right shoulder injury ended his season.
The Dolphins courted Denver's Kyle Orton this summer before deciding to stay with Henne, who has been much maligned since becoming Miami's starter in 2009. Henne was jeered by fans during training camp but showed some improvement this season, looking more decisive and winning praise for his leadership.
"He has done a tremendous job and has really improved," Sparano said. "It's unfortunate because I know the kid really wanted to see this whole thing through."
Even with his progress, Henne ranks 24th in the NFL in passing efficiency, and Miami scored only one touchdown each of the past three games.
A second-round draft pick in 2008, Henne has thrown 31 touchdown passes and 37 interceptions in 36 games. As a starter he's 13-18.
Coincidentally, the last time the Dolphins played at San Diego, they lost quarterback Chad Pennington with a season-ending shoulder injury. That was in September 2009, and Henne made his first start the following week.
"When you lose your starting quarterback -- the guy takes a ton of reps, and the next guy doesn't," Sparano said. "When you're in the middle of the season, to catch those people up on reps, that's hard to do."
Information from ESPN NFL Insider Adam Schefter, ESPN senior NFL analyst Chris Mortensen, ESPN.com senior NFL writer John Clayton and The Associated Press was used in this report.