The team announced the move Tuesday, shortly after the NFL's free agency period opened, and a day before Fitzpatrick was due a $3 million bonus.
"We kept every possible option open right down to the wire, when we had to make a decision on whether to keep Ryan," general manager Buddy Nix said. "In the end, we had to do what we feel is best for our football team. And it was a difficult decision."
Fitzpatrick's up-and-down performance and his expensive contract were factors in his release. He went 20-33 as a starter over four seasons in Buffalo. And he was in the midst of a six-year, $59 million contract extension signed in October 2011.
That was regarded as too expensive for a player who wasn't guaranteed to return as a starter this season. The Bills had held out hope that Fitzpatrick would be open to restructuring his contract, and free up space under the salary cap to allow the team to pursue free agents, and re-sign its own players.
A change in coaches didn't help Fitzpatrick, either. Marrone took over in January after Chan Gailey was fired after three straight losing seasons. Gailey was regarded as Fitzpatrick's biggest supporter.
Fitzpatrick wasn't available for comment. He had spent the past two months with his family in their offseason home in Arizona.
The move leaves Buffalo with one experienced quarterback on its roster -- Tarvaris Jackson, who re-signed to a one-year contract last month. Nix already has expressed an intention to select a quarterback in the draft next month. The Bills also had been linked to Alex Smith, before the former 49ers starter was traded to Kansas City two weeks ago.
"Our focus remains on adding another quarterback to our roster, and we will continue to explore every option available to us," Nix said.
The Bills had sent mixed signals regarding Fitzpatrick's future over the past month.
His status appeared to be secure in mid-February, when Marrone announced he informed Fitzpatrick and Jackson that he intended to have both compete for the starting job this offseason. The Bills' message was less definitive a little over a week later at the NFL combine in Indianapolis. That's where both Nix and team president Russ Brandon were evasive when discussing Fitzpatrick.
Already on their sixth coach since 2000, the Bills are in the midst of their latest quarterback shuffle. They've now had nine quarterbacks start at least eight games since Hall of Famer Jim Kelly retired after the 1996 season.
The Bills haven't had a winning season since going 9-7 in 2004. And they've gone 13 seasons without a playoff berth, the NFL's longest active drought.
Fitzpatrick took over the starting job three weeks into the 2010 season, after Trent Edwards was benched and then released a week later. Fitzpatrick was rewarded with his current contract while helping the Bills get off to a surprising 5-2 start a year later.
The Bills, however, unraveled by losing nine of their final 10 games, and went 6-10 again last year.
Not all the blame could be laid on Fitzpatrick, the Harvard graduate, who was selected in the seventh round by St. Louis in the 2005 draft.
In Buffalo, he joined Kelly last year in becoming only the second Bills quarterback to throw 24 touchdowns in three consecutive seasons. Fitzpatrick, however, could never erase questions about his inconsistency. In 55 games in Buffalo, he's thrown 80 touchdowns and 64 interceptions, including a career-worst 23 in 2011.
He finished his career in Buffalo ranking third on the team list in touchdowns, and fourth with 11,654 yards.