The running back has not played since injuring in his foot in a win over the Indianapolis Colts back in Week 8.
Henry endured a frustrating spell on the sidelines following surgery, but is back for the Divisional Round showdown with the fourth-seeded Bengals at Nissan Stadium.
The 2020 NFL Offensive Player of the Year came through contact training this week and is ready to make a timely comeback.
Henry said: "I felt great. I just wanted to get some pads on. Haven't had them on in a while and got some contact going."
The two-time Pro-Bowler rushed for 937 yards and 10 touchdowns in 219 carries in his eight regular-season games for the top-seeded Titans this season.
Henry was leading the league in rushing when he sustained the injury.
He made 112 yards from 18 carries, scoring one touchdown when the Titans last faced the Bengals in November 2020, a game that was won 31-20 by Cincinnati.
The Titans improved to 6-2 with their 34-31 overtime victory in Indianapolis on Sunday.
However, it may have come at a massive cost, with ESPN's Adam Schefter reporting Henry could now miss the remainder of the campaign.
Subsequent reports have revealed Henry is believed to have broken a bone in his foot and is set to undergo an MRI scan.
It is tough to oversell Henry's importance to the Titans, who have leaned on the running back as the undisputed focal point of their offense for the last three seasons.
This season, Henry has produced consistency to put him in position to threaten Eric Dickerson's record for rushing yards in a single season.
He leads the NFL with 947 yards, 288 more than his nearest challenger, the Colts' Jonathan Taylor.
Averaging 117.1 yards per game, he is on pace for 1,990, though several more performances of 100 yards or more could put him within striking distance of the 2,105 Dickerson racked up in 1984.
Now that record seems set to stand, with the AFC South-leading Titans likely to put more of the burden on quarterback Ryan Tannehill in Henry's absence.
Henry had continued to deliver despite a workload that would see lesser running backs break down under the strain.
He carried the ball a league-leading 303 times in 2019 and increased that number to 379 last season, winning the rushing title in back-to-back years.
The former Alabama star had already tallied 219 rush attempts this season, with backup Jeremy McNichols used predominantly as a pass-catcher.
Tennessee will not lean on McNichols or Darrynton Evans in the same way, meaning the onus will be on Tannehill to lead the Titans on what they hope will be a deep playoff run.
The star running back is reported to have suffered a broken bone, with Titans coach Mike Vrabel saying Henry will "work extremely hard to get back".
The Titans have leaned on Henry as the focal point of their offense for the last three seasons and his absence will come as a major setback.
Tennessee improved to 6-2 with their 34-31 overtime victory in Indianapolis on Sunday, but Henry was placed on injured reserve a day later.
"Derrick is going to have surgery in the morning [on Tuesday]," Vrabel said, quoted on the Titans' official website. "We are not going to put a timeline on when he may return.
"I know that he'll do everything that he can to work himself back, to be able to help this football team. And whenever that is, that's when it will be."
This year, Henry has produced consistency that was putting put him in position to threaten Eric Dickerson's 1984 record of 2,105 rushing yards in a single season.
He leads the NFL with 937 yards, 288 more than his nearest challenger, the Colts' Jonathan Taylor.
Henry carried the ball a league-leading 303 times in 2019 and increased that number to 379 last season, winning the rushing title in back-to-back years.
The former Alabama star had already tallied 219 rush attempts this season, putting him way out ahead in the NFL, with backup Jeremy McNichols used predominantly as a pass-catcher.
Vrabel said: "We'll have to move on unfortunately without him in the short term, and not look back. I hate to speak for our players, but Derrick is disappointed, everybody is.
"We spent a lot of time together with the coaching staff and with the players, so you never want to see any of them injured in any capacity. So I know that Derrick is going to work extremely hard to get back to do everything he can to help this football team."
Dickerson's record no longer appears to be in any danger, and the AFC South-leading Titans are likely to put an increased burden on quarterback Ryan Tannehill in Henry's absence.
Henry was earlier designated to return from injured reserve, opening his 21-day window to be placed back on the active roster.
The star running back suffered a fractured foot in the Titans' overtime win against the Indianapolis Colts back on October 31.
Henry, who won the rushing title in 2019 and 2020, has 937 yards on 219 attempts with 10 touchdowns in the 2021 season.
Despite his return to practice, it appears unlikely he will be ready to feature in the Titans' regular-season finale against the Houston Texans, in which they could clinch the number one seed in the AFC.
However, should Tennessee indeed secure top spot in the conference, it will give the Titans a first-round bye and Henry extra time to recover for a home game in the Divisional Round.
Even with Henry missing half the season, the Titans still rank third in rush yards per game with 142.5 and will hope his return to their ground attack can help propel them to a second Super Bowl appearance in franchise history.
The move ensures 2019 Pro Bowler and Titans star Henry is officially under contract for the 2020 season.
Tennessee have until July 15 to negotiate a long-term deal to replace the franchise tag.
On Wednesday, Titans general manager Jon Robinson said: "I think any time a player, when you have to use the tag on them, that's something that ideally they probably don't want.
"But still, at the same time, I know that he wants to be a part of this football team and I thought it was good that they communicated back he does want to be here, and he does want to keep working on this thing.
"It wasn't something like, 'OK, well, I'll take the [tag] and I'm done, or I am just going to do whatever.' He wants to be here, and he conveyed the message to me, through his agent, that he wants to keep working on this thing and we do, too."
Henry led the NFL in rushing in 2019, finishing the regular season with 1,540 yards and 16 touchdowns as Tennessee made the playoffs.
The 26-year-old also played a pivotal role in their run to the AFC Championship Game, going for 182 and 195 yards respectively in upset road wins over the New England Patriots and the Baltimore Ravens.
So while the soap opera between Dak Prescott and the Dallas Cowboys gets to air another year after the two sides failed to work out a contract that would have put the talented quarterback among the NFL's highest-paid players, a few other teams were busy locking up vital players amid less fanfare.
Derrick Henry will still be pounding the rock for the Tennessee Titans for the foreseeable future, the Cleveland Browns made Myles Garrett the league's highest-paid defensive player and the Kansas City Chiefs will have defensive lineman Chris Jones on board for what should be an extended window for another Super Bowl run.
When breaking down those aforementioned agreements, it appears all three teams were able to get good value even in what's arguably been the most volatile offseason in league history.
Let's start with Henry. On the surface, the four-year, $50 million contract the Titans gave the 2019 NFL rushing champion looks rather risky considering the often short shelf life of running backs and how a similar pact the Los Angeles Rams constructed with Todd Gurley two summers ago spectacularly backfired.
But Tennessee wisely front-loaded the deal, with most of the $25.5 million in guarantees on the books for the first two seasons, and can cut bait without much penalty after 2021 in the event Henry begins to show a steep decline.
It's not hyperbole to suggest that Ryan Tannehill's breakthrough 2019 season was a direct result of the threat Henry presented to opposing defenses as a runner. By extending their most important player, the Titans have not only given their quarterback his best chance to succeed, they've increased their chances of again contending for an AFC title for at least the next two years.
Of course, the road to an AFC championship still figures to go through Kansas City following the reigning Super Bowl champions' massive recent spending spree that resulted in 2018 NFL MVP Patrick Mahomes landing a record 10-year extension worth up to $503 million and Jones agreeing to a four-year, $80 million deal.
The Chiefs will have some tough decisions to make to get under the salary cap once the big money in Mahomes' contract kicks in after this season, but they've rightfully identified Jones, whose 24.5 sacks over the last two seasons trails only Aaron Donald for the most among interior defensive linemen, as a player to keep.
And the 2019 Pro Bowler gets the benefits of some long-term security and the chance to reach free agency at the relatively young age of 30 - not to mention the opportunity to realistically add a few more rings to his collection.
Extending Garrett may not have been an urgent matter for the Browns, as the 2017 number one overall pick still had two seasons remaining on his rookie contract, but the five-year, $125 million extension was a shrewd, forward-thinking move by new general manager Andrew Berry.
Sure, $25 million a year for a non-quarterback is a lot of coin, but Cleveland has the most cap space in the league right now and with the way the pass-rusher market has been trending, that annual salary could be a relative bargain down the road if Garrett continues to produce double-digit sacks towards the latter end of the deal.
After years and years of bumbling leadership hires, the Browns just maybe have finally gotten it right this winter with the additions of two impressive young minds in Berry and new coach Kevin Stefanski.
It's still way too early to gauge the impact the coronavirus will ultimately have on the NFL's economic landscape in the coming years, but the Titans, Chiefs and Browns at least appear to have positioned themselves well for the potential pitfalls that may lie ahead.
The Titans had until 16:00 ET to reach an agreement with the 2019 NFL rushing leader, who previously accepted his franchise tender and would have earned $10.3m this season without a new contract.
Henry's new deal is the fourth-largest active contract for a running back, behind only Dallas' Ezekiel Elliott (six years, $90m), Carolina's Christian McCaffrey (four years, $64m) and the New York Jets' Le'Veon Bell (four years, $52.5m).
The 2015 Heisman Trophy winner earned his big payday by leading the NFL with 1,540 rushing yards and tying for the league lead with 16 rushing touchdowns during a breakout 2019 regular season. Henry then helped Tennessee advance to the AFC Championship game by rushing for a combined 377 yards in the Titans' upset playoff wins at the New England Patriots and Baltimore Ravens.
Henry's rushing yardage total was the fourth-highest in a season in franchise history, and the most since Chris Johnson led the NFL with 2,006 in 2009.
A second-round pick by Tennessee in the 2016 draft, Henry is the second significant offensive player the team has locked up with a long-term deal this offseason. The Titans were able to re-sign starting quarterback Ryan Tannehill to a four-year, $118m contract in March.