Near the end of his reign, the 2.03 TV rating for the June 13 episode of Raw which he appeared in was the lowest since March 3, 1997. At Money in the Bank on June 19, Reigns was defeated cleanly by Rollins marking his first clean loss on the main roster, ending his title reign at 77 days. On June 21, Anoaʻi was suspended for 30 days for his first violation of WWE's Wellness Program and, in response, he apologized on Twitter. WWE's Wellness Program uses drug testing to detect substance abuse. Pro Wrestling Torch and TheWrap reported that WWE knew of Anoaʻi's violation before Money in the Bank, leading to Reigns being scripted to lose his world title at the event.

Anoaʻi played football for three years at Pensacola Catholic High School and one year at Escambia High School. In his senior year, he was named Defensive Player of the Year by the Pensacola News Journal. He then attended Georgia Institute of Technology, where he was a member of the Georgia Tech Yellow Jackets football team along with Calvin Johnson, who later became a wide receiver in the National Football League (NFL). Anoa'i was a three-year starter beginning in his sophomore year and was also one of the team captains as a senior. Anoa'i was named to the first-team All-Atlantic Coast Conference (ACC) after recording twenty-nine tackles for loss and twelve sacks in 2006.

After going undrafted in the 2007 NFL draft, Anoa'i was signed by the Minnesota Vikings in May 2007, but was released later that month. The Jacksonville Jaguars signed him in August 2007, only to release Anoa'i less than a week later before the start of the 2007 NFL season.

In 2008, Anoaʻi was signed by the Edmonton Eskimos of the Canadian Football League (CFL). Wearing the number 99, Anoaʻi played for one season with the Eskimos, featuring in five games, of which he started three. Anoaʻi's most notable game came against the Hamilton Tiger-Cats in September, where he tied for the team lead with five tackles and had a forced fumble. Anoa'i was released by the Eskimos on November 10, and proceeded to retire from professional football.

Anoa'i made his first venture into wrestling in July 2010, when he signed a developmental contract with World Wrestling Entertainment (WWE) and was later assigned to their developmental territory Florida Championship Wrestling (FCW). He debuted on September 9, 2010, using the ring name Roman Leakee (often shortened to Leakee), in a loss to Richie Steamboat in a singles match. Further losses to Idol Stevens and Wes Brisco ensued, before he gained his first win on September 21 over Fahd Rakman. He continued competing in FCW throughout the remainder of the year, wrestling mainly in tag team matches. On the January 16, 2011 episode of FCW television, Leakee was a competitor in a 30-man Grand Royal, but was eliminated. Later in 2011, Leakee formed a tag team with Donny Marlow and the pair unsuccessfully challenged Calvin Raines and Big E Langston for the FCW Florida Tag Team Championship on July 8.

Reigns debuted on the company's main roster in November 2012 (having performed in its developmental system from 2010) as part of stable The Shield and during this time his character was well received by critics. During 2014 Royal Rumble match, the live crowd cheered for Reigns over eventual winner Batista, despite Reigns being a villain character.

Reigns made his main roster television debut as on November 18 at Survivor Series alongside Dean Ambrose and Seth Rollins, assaulting Ryback during the triple threat main event for the WWE Championship, allowing CM Punk to retain the title. The trio declared themselves The Shield and vowed to rally against "injustice", while also denying working for Punk, even though they would routinely emerge from the crowd to attack Punk's adversaries, including Ryback and WWE Tag Team Champions Team Hell No (Daniel Bryan and Kane). This led to a six-man tag team Tables, Ladders, and Chairs match at TLC: Tables, Ladders & Chairs on December 16, in which Reigns, Ambrose and Rollins defeated Team Hell No and Ryback in their debut match. The Shield continued to aid Punk in January 2013, attacking both Ryback and Reign's real-life cousin The Rock. On the January 28 episode of Raw, it was revealed that Punk and his manager Paul Heyman had been paying The Shield and Brad Maddox to work for them.

Anoaʻi married Galina Joelle Becker in early December 2014. He has a daughter named Joelle, with whom he appeared in a public Service announcement in June 2014. His wife, Galina, gave birth to twin boys in 2016.

With WWE unrelenting in their multi-year effort trying to establish Reigns as a mega-star, Reigns was booed at various WWE events, most notably at major pay-per-view events (where he wrestled in the main event in) such as 2015's WrestleMania 31, 2016's Royal Rumble and WrestleMania 32, as well as the 2017's Royal Rumble. As a result, critics observed WWE's repeated attempts to edit out and conceal hostile fan responses in 2015–2017, while Reigns was named as 2016's "Most Hated Wrestler of the Year" by Pro Wrestling Illustrated, becoming the first Babyface Wrestler to have been recognized as such. In 2016, WWE Hall of Famers Stone Cold Steve Austin, Rikishi and Hulk Hogan encouraged WWE to turn the Reigns character into a villain and after his suspension Yahoo! TV also urged WWE to "quit pretending he's some kind of lovable underdog" with a villainous turn.

On July 19 at the 2016 WWE draft, Reigns was drafted to the Raw brand. Despite Reigns' suspension, WWE continued to advertise Reigns as part of the Battleground main event, and went on to acknowledge Reigns' suspension on television. On July 24 at Battleground, Reigns made his televised return, facing Rollins and Dean Ambrose (whom Rollins dropped the title to at Money in the Bank after Ambrose cashed-in his Money in the Bank contract) for the now-renamed WWE Championship, but Ambrose successfully retained the championship when he pinned Reigns in a clean finish. The following night on Raw, Reigns also failed to contend for the newly announced WWE Universal Championship against Rollins at SummerSlam, as he lost to the debuting Finn Bálor after earlier winning a fatal four-way match that involved Chris Jericho, Sami Zayn and Sheamus.

Anoaʻi is half Samoan and half Italian. Both his father Sika Anoaʻi and his brother Rosey, who died on April 17, 2017, were professional Wrestlers. As a member of the Anoaʻi family, he is a cousin to former professional Wrestlers Yokozuna, Rikishi, Umaga, The Tonga Kid and first cousin once-removed to The Usos and The Rock (non-biological).

In January 2018, Richard Rodriguez, who was arrested for distributing steroids internationally, gave an interview where he identified Anoaʻi as being involved in a steroid ring under Rodriguez's company Wellness Fitness Nutrition. Anoaʻi released a statement denying hearing of Rodriguez or Wellness Fitness Nutrition.