Landry suffered a sprained medial collateral ligament in the first quarter of the Browns' 31-21 win over the Houston Texans on Sunday.
Having been placed on IR, Landry now must miss at least the next three games before being allowed to return to action.
That rules him out of Sunday's home game with the Chicago Bears and the trips to face the Minnesota Vikings and Los Angeles Chargers.
And, with Odell Beckham still yet to make his 2021 debut as he recovers from a torn anterior cruciate ligament, the Browns suddenly look thin at the receiver position.
There is reportedly a good chance Beckham will be ready to face the Bears, but Landry's absence means there will be more pressure on Donovan Peoples-Jones, Rashard Higgins and rookie Anthony Schwartz to produce for Cleveland.
Landry caught all five of his targets for 71 yards in the Browns' opening loss to the Kansas City Chiefs before hauling in one pass for nine yards against the Texans.
He finished last season with 72 catches for 840 yards and three touchdowns.
The Browns can afford to have faith in Higgins, who in 2020 was third among wide receivers in burn percentage. Higgins won his match-up with a defender on a play where he was targeted 78.4 per cent of the time.
Higgins was also seventh with a big-play percentage of 43.3. Peoples-Jones (42.6 per cent) was ninth in that metric and finished the year third with 17.11 burn yards per target, albeit across the small sample size of 20 targets.
The Browns agreed a deal for Amari Cooper from the Dallas Cowboys on Saturday and had permitted Landry to seek a trade.
However, no deal was forthcoming for the 29-year-old, who was due to make $14.3million in base salary, and so he has been granted his release.
It is expected to clear $14.9m in cap space for the Browns, and cost around $1.5m in dead cap.
Landry had a frustrating 2021, playing just 12 games due to injuries and contracting COVID-19, making two touchdowns and catching 52 passes for a season total of 570 yards.
However, he was otherwise a near ever-present for Cleveland since arriving from the Miami Dolphins in 2018, making more than 80 receptions in each of his first two seasons and receiving for a total of 1,174 yards in 2019.
Arguably his finest game for the Browns came in the 40-25 win over the Baltimore Ravens in that season as he made eight catches for 167 yards, the best single game numbers of his career.
Speaking to the Browns' website, executive vice president and GM Andrew Berry said: "The trade for Jarvis Landry in 2018 was a key moment for our organisation.
"Jarvis' on-field production and fiery competitiveness speaks for itself, but his leadership and team-oriented attitude impacted our culture in a way that will last in time even beyond his release. These decisions are always difficult, but we wish Jarvis well and we look forward to the day when he returns as a storied Browns alumnus."
Landry's best career season came in 2017 with Miami as he led the league with 112 receptions.
Landry was saddled by a hip injury all of last season after getting injured in training camp.
Despite being slowed, he still managed to lead the Browns with 83 receptions, 1,174 receiving yards and six receiving touchdowns to earn a fifth Pro Bowl selection.
"Rehab process is going great," Landry said on Wednesday on a Zoom call from his home in Florida.
"It's just a little difficult obviously, just some of the modality type of things I've been doing that obviously with quarantine and everything I haven't been able to have access to. So that's kind of been the toughest part of it.
"Right now I'm a little bit ahead of schedule, but the most important thing right now is taking it day by day. I can't predict when exactly I'll be on the field, whether that's July, August or September. But obviously my return date is sometime in August."
Landry originally considered against having surgery and gutting out another season playing with pain before opting to go under the knife following the Pro Bowl in February.
He said on Wednesday that having surgery was "absolutely" the right decision.
"It was something I knew I needed," the 27-year-old said. "I was going to try and put off and play the tough guy for one more year. But just understanding where I was, the things it was not allowing me to do, I did not want to be part of the reason for the team not having success."
Rehab from the surgery was expected to take six to eight months, which puts his availability for the 2020 season opener in question.
Landry, though, is motivated to extend his games played streak and sees himself being ready for training camp, when players are cleared to practice amid the coronavirus pandemic.
"That's one of the goals that I would set out for myself since I was a kid watching 'Monday Night Football'," he said.
"And it's still something that's in the back of my mind. Obviously I want to make sure that I'm going through this process the right way, too, and making sure that I'm healthy enough to be able to go out there and help the team win games and not hurt the team."
Landry, 29, has the third-most receptions and fourth-most targets in the entire NFL since his arrival in 2014.
Drafted in the same year as arguably the best receiver in the league, Davante Adams, Landry has 19 more catches (688 to 669) and 33 more targets (1,045 to 1,012) in just seven more career games (123 to 116).
The five-time Pro Bowler has spent the past four seasons with the Browns after playing his first four years with the Miami Dolphins, but his production tailed off badly in 2021, posting career-lows in games played, targets, receptions, yards and touchdowns as the Browns sputtered.
Landry joins a receiver group in New Orleans consisting of new first-round draft pick Chris Olave, and 2019 Offensive Player of the Year Michael Thomas, who missed the entire 2021 season with a serious ankle injury but is expected to be back in action at the start of the 2022 campaign.
The Saints also boast one of the best running backs in the NFL in the form of Alvin Kamara, and with quarterback Jameis Winston returning from a torn ACL, new head coach Dennis Allen may have the makings of a well above average offense.
It is a homecoming for Landry, who grew up in Louisiana and attended Louisiana State University.
He may not be at the Super Bowl for the first time in four years, but Brady ensured he remained the focus in Miami with an uncaptioned black-and-white photo he uploaded to his social media accounts on Thursday.
Six-time Super Bowl champion Brady, who could be seen walking in the tunnel at the Patriots' stadium in the picture, is due to become a free agent this offseason and the 42-year-old has indicated he wants to carry on playing.
The possibility of him starting his 21st NFL season away from New England is therefore seemingly a realistic possibility.
"Oh, that means he's out the door," Los Angeles Rams cornerback Ramsey said when shown the tweet.
"He's out the door. He's definitely out the door. He's gone from New England. That's exactly what that means."
The Los Angeles Chargers and Indianapolis Colts have been mooted as potential destinations for Brady.
Though when asked where he thought Brady could wind up, Ramsey added: "I don't know, the [Las Vegas] Raiders maybe."
Philadelphia Eagles wide receiver Jackson interpreted the tweet in another way, believing Brady is about to hang up his cleats after 20 glorious years with New England.
"He's walking away. He's retiring," said Jackson, who, like Ramsey, was speaking at the EA SPORTS Bowl.
"I don't know, man, he's walking out the tunnel, man. He's leaving. I'm surprised you don't see a deuce sign!
"I don't know, he's playing with you, man. He's playing with you."
New York Jets Pro Bowler Jamal Adams had implored Brady to "please leave the AFC East!", yet Jarvis Landry, who plays in the AFC North for the Cleveland Browns, feels it would be strange to see the veteran in a different jersey.
"It's not right to take the Patriots out without Tom Brady there," Landry added.
"Like, does it even count anymore? You know what I mean?
"I'm kidding. But, you know, he's a true competitor.
"I'm sure whatever decision that he makes is going to be the right one for him and he's going to make it work."
As they chase a ticket to the postseason, the 7-6 Browns are poised to have to rely on backups at a critical moment, with their ranks suddenly severely depleted.
It was revealed on Tuesday they have lost wide receiver Jarvis Landry, guard Wyatt Teller, tight end Austin Hooper, left tackle Jedrick Wills and defensive end Takkarist McKinley for now. Drew Forbes was named on the same list, with wide receiver JoJo Natson and tight end Ross Travis also sidelined.
The NFL.com website reported all have tested positive for the coronavirus. The Browns have not officially confirmed that to be the case.
Browns head coach Kevin Stefanski said meetings with players, virtual rather than in person, would take place during Tuesday afternoon.
He backed his squad to show they have sufficient quality to ride out the situation.
Stefanski said in a news conference: "We've seen, through last season, have seen it this year, guys step up. That's what the NFL's about. You're without guys due to injury or otherwise and guys step up. And that's why we have a bunch of players on this team that we trust."
It remains to be seen whether David Njoku, Anthony Walker Jr and punter Jamie Gillan, who all missed the 24-22 win over the Baltimore Ravens on Sunday due to being on the reserve/COVID-19 list, will be available for the game with the 6-7 Raiders.
Stefanski said, quoted on cleveland.com: "I don't have an update on those guys in particular. Again, we'll just follow the protocols on each one of them and then we're just going to focus on today. I think that's the prudent thing to do and make sure we do a great job with our virtual meetings, do a great job with this walkthrough."
Veteran wide receiver Beckham was released by the Browns last week, a move that came after his father complained on social media about his lack of involvement in the team's offense.
Beckham Sr posted an 11-minute video on Instagram, highlighting moments he felt Browns quarterback Baker Mayfield had failed to find his son.
Mayfield later stated he considered Beckham a "good friend" and wished him well.
Three-time Pro Bowler Beckham was sidelined with a torn ACL in 2020 and made 17 catches for 232 yards and zero touchdowns in six games for the Browns this season, before signing for the Los Angeles Rams.
For Landry, the exit of his friend is something that remains difficult to accept.
"It definitely was something that hurt. It stung. It still does," Jarvis said in quotes reported by the Akron Beacon Journal.
Mayfield's own form has been under scrutiny as he battles several injury complaints. Already contending with a left shoulder issue that may require surgery down the line, Mayfield has a sore foot and now a contusion on his right knee.
He threw for only 73 yards as the Browns were hammered 45-7 by the New England Patriots over the weekend but Landry leapt to the defence of his teammate.
"He's a tough man, and he's doing all the things necessary to make sure that he can be out there with us," Landry said.
"As playmakers, when the ball's in the air, we're doing our best and understanding and knowing that it's the situation where he's got to get healthy, but we're still out here making plays with each other, for each other, and he always gives his best.
"That's all you can ask for."
Landry has himself had issues this season, missing four games due to a knee sprain.
"I haven't been able to get the ball so much, either," he said.
"But at the end of the day I've been able to [make the most] with the opportunities I'm given.
"Yeah, I'm battling some things, but on Sundays I always give everything I have. And that will never change."
The Browns (5-5) are fourth in the AFC North and face the winless Detroit Lions on Sunday.