Athletic director Jack Swarbrick announced the decision to fire Weis on Monday, saying in a news release: "We have great expectations for our football program, and we have not been able to meet those expectations"
"As an alumnus, Charlie understands those goals and expectations better than most, and he's as disappointed as anyone that we have not achieved the desired results."
Swarbrick said he recommended to university president the Rev. John Jenkins on Sunday night that Weis be let go with six years left on his contract. Weis finishes with a 35-27 record in five seasons, among the worst of any Fighting Irish coach.
Assistant head coach Rob Ianello will step in for Weis until a new coach is hired.
The Fighting Irish (6-6) are eligible to play in a bowl game, but Swarbrick has said he wants to hear from the players before deciding if Notre Dame will go to a minor postseason game.
Following a 6-2 start this season, Notre Dame's losing streak began with the second upset by Navy in three years. Then came losses to Pittsburgh and to Connecticut in double overtime on senior day in South Bend. By the time the Irish lost their season-finale to Stanford on Saturday, it seemed inevitable Weis would be gone.
Speculation about possible replacements for Weis has been rampant for weeks. Among the top names mentioned, Florida's Urban Meyer and Oklahoma's Bob Stoops already have said they plan to stay where they are.
Speaking on a conference call Monday, Stoops said: "I'm going to be at Oklahoma next year, so I can't be at two places at once."
Cincinnati's Brian Kelly has also been mentioned, along with Stanford's Jim Harbaugh and TCU's Gary Patterson.
A brash offensive coordinator with the NFL champion New England Patriots when he was hired, Weis raised Irish expectations with back-to-back appearances in BCS bowl games in his first two seasons.
Since then, though, Notre Dame has gone 16-21 - the most losses by the Irish in a three-year span.
Weis' record is worse than his two predecessors, Tyrone Willingham and Bob Davie, who also were fired. Notre Dame is now looking to hire its fifth coach this decade.
Weis received a new 10-year contract midway through his first season, shortly after a thriller against top-ranked USC that ended in a 34-31 Notre Dame loss.
Even though the Irish fell short, playing even with Matt Leinart, Reggie Bush and the mighty Trojans had the Notre Dame faithful hopeful they had found a coach capable of returning the program to its past glories. The Fighting Irish have won eight AP national titles, more than any other school, but none since 1988.
But the USC loss turned out to be the highlight of Weis' tenure. Because it began so promisingly, Weis' final three seasons in South Bend were especially painful for the legion of Fighting Irish supporters nationwide.
Weis came to Notre Dame brimming with confidence after serving as offensive coordinator for the three-time Super Bowl champion Patriots.
The first two seasons under Weis produced more victories (19) than any other Notre Dame coach, including the greats such as Knute Rockne, Frank Leahy and Ara Parseghian. Both seasons, though, ended with BCS bowl losses.
Asked about his start at the time, Weis said: "I really haven't done anything yet." And his best days at Notre Dame were already behind him.
"There were a lot of expectations he didn't live up to. He admitted to that," said former Notre Dame wide receiver David Grimes, who played four seasons for Weis and was on campus working out Monday. "But it's sad to see."
With Brady Quinn, Jeff Samardzija and other key players gone in 2007, the Irish started 0-5 for the first time in school history. They finished 3-9, leaving Weis one loss shy of matching Davie's school record of 16 losses in his first three seasons.
Most shocking, though, was the fact the Irish finished last in the NCAA in total offense just three years after Weis said at his introductory news conference that when it comes to X's and O's "we have the greatest advantage."
The past two seasons the Irish have collapsed in November. They got off to a 5-2 start before going 1-4 down the stretch a year ago. This year they ended the season with four tough losses.
"I'm disappointed," former Notre Dame player Asaph Schwapp said. "It's definitely sad to see. I loved being coached by him."
Notre Dame fans who celebrated Weis' cockiness when he was winning grew tired of his Jersey attitude when the Irish started losing, with many calling him arrogant.
His biggest failure, however, was his team's inability to play good defense. The Irish never finished higher than 39th in the country in total defense and gave up big play after big play.
Weis appeared to know his firing was imminent, saying a day after the loss to Connecticut on Nov. 21 that he would have a hard time arguing against his dismissal "because 6-5 is not good enough" - an echo of his words when he took the job.
Overall, Weis' teams lost six games by 26 points or more. That's the same number Willingham had in three seasons. Davie only had one such loss and Lou Holtz, the last coach to bring a national title to South Bend, didn't have any. Weis had a pair of 38-0 losses to Michigan and USC.
Whoever replaces Weis will be charged with ending the longest title drought in school history.