Noted for his success at every stage of his career, he is the only player to have rushed for at least 2,000 yards in a season at the high school, college and professional levels.

[6] Henry's father was absent for much of his childhood, having been arrested 20 times for various crimes including drug and prostitution-related offenses, and was consequently in and out of prison and had trouble maintaining employment.

Henry was raised primarily by his grandmother, Gladys, who nicknamed him "Shocka", as his birth shocked the whole family, given his parents' young ages.

He was so big and powerful for his age that a copy of his birth certificate was brought to all of his games, and even then, opposing parents skeptically shook their heads.

[23] He held offers from many of the top college football programs in the country, including USC, Notre Dame, Tennessee, Florida, and Clemson.

[28] That same day, he published an article in The Players' Tribune thanking his late grandmother for the inspiration to continue pursuing his degree.

[28][29] As a true freshman in 2013, Henry rushed for 382 yards on 36 carries with three touchdowns in a backfield largely dominated by T. J. Yeldon and Kenyan Drake.

[33][34] In that game, Spanish-language broadcaster Pablo Viruega on ESPN Deportes nicknamed him "El Tractorcito" (The Little Tractor) due to his long stride and powerful gait.

[42] Alabama qualified for the College Football Playoff and faced off against Ohio State in the National Semifinals in the Sugar Bowl.

Scouts regarded his main assets to be his large frame, violent running, ability to break tackles with ease, speed, long strides, superior conditioning, and consistent play.

[84] On October 16, 2017, on Monday Night Football, Henry ran for a then career-best 131 yards on 19 carries, including a 72-yard touchdown late in the fourth quarter of the 36–22 victory over the Indianapolis Colts.

[93] During the 2018 offseason, Matt LaFleur was hired as the Titans' new offensive coordinator and the team also acquired running back Dion Lewis.

During Week 2, Henry recorded an eight-yard pass completion, the first of his career, to wide receiver Taywan Taylor in the Titans' 20–17 victory over the Texans.

In a cold and rainy game, Henry led the NFL in rushing for the second consecutive week with 170 yards and two touchdowns on a career-high 33 carries, along with a one-yard reception and six-yard pass completion in the 17–0 shutout.

[121] During the regular-season finale against the Texans, Henry finished with 211 rushing yards and three touchdowns as the Titans won 35–14 and made it to the playoffs as a wild-card team.

[130] During the Divisional Round against the Baltimore Ravens, Henry rushed 30 times for 195 yards and threw a three-yard touchdown pass to wide receiver Corey Davis in the 28–12 road victory.

[155] During a Week 8 win against the Colts, Henry suffered a Jones fracture that would end up sidelining him for the remainder of the regular season.

[174] In the Week 18 winner-take-all game for the AFC South, Henry had 30 carries for 109 rushing yards in the 20–16 elimination loss to the Jacksonville Jaguars.

[210] Standing at 6 feet 3 inches (1.91 m) tall and weighing 247 pounds (112 kg), Henry is much larger than most running backs and has a frame comparable to that of a linebacker.

[211] Henry is a "power back", using his large size and strength to overpower defenders, stiff arm and break tackles.

In 2019, Henry founded the Two All Foundation to level the playing field for today’s youth so that their future success is not limited by the circumstances of their upbringing, background, disability or influence.

[278] Reportedly, Henry spends over a quarter of a million dollars annually on body maintenance, which includes massages, hyperbaric oxygen, infrared saunas, and a personal chef, to keep himself in prime condition and peak shape.

He also receives IVs with vitamins and nutrients three times a week and maintains a stringent diet, avoiding gluten, artificial sugar, fried foods, and dairy.

[281][282] Each December, Henry and his family, along with volunteers from the Two All Foundation, host an annual holiday giveaway in Yulee, where they distribute hundreds of toys to the first 500 children who attend.

[284] When Nashville firefighter Jeremy Taylor and his family lost their home and belongings in March 2021, Henry stepped in to offer support, donating $10,000 to help assist them.

In September 2021, Henry partnered with the Boys & Girls Club of Middle Tennessee to host a back-to-school event, another annual occurrence.

Thanks to sponsors and Henry’s personal donations, they met the goal of providing 5,000 backpacks with school supplies, plus $50 gift cards for 25 children in need.

Henry also took these 25 kids on a shopping trip, giving them $100 gift cards and sharing his own Boys & Girls Club journey.

[286] In September 2023, Henry purchased Nike shoes for 60 children from the Boys and Girls Club, which were delivered earlier that month.

[288] Not long after, he held a back-to-school event at Curtis Bay Elementary, providing 200 students with backpacks and essential supplies.