Tyrann grew up in the Central City area of New Orleans, where he was raised by his grandparents. His mom was always busy, and his father spent the largest part of his life in jail after being sentenced for murder. When his grandfather died in 1997, Tyrann has been adopted by his uncle, Tyrone Mathieu, and his aunt, Sheila Mathieu.

Tyrann went to “St Augustine High School”, and he played on the high school football team, the “St Augustine Purple Knights”. He achieved 32 tackles, one sack, and five interceptions with one fumble recovery in his senior year. He also ran track for St Augustine and was part of the relay team for the school. He was a top performer in the high jump and was able to make 7.29 meters in a long jump. He was ranked 13th in the country as a cornerback by Rivals.com, and he is considered to be a four-star recruit.

Tyrann has been given an athletic scholarship to attend the “Lousiana State University”, and he played for coach Les Miles’ “LSU Tigers Football” team from 2010 to 2011. In his freshman year in 2010, Tyrann played in all 13 games with one start. He completed the season scoring 59 tackles, 3 sacks, and 2 interceptions. He’s been named the “Most Outstanding Defensive Player” of the 2011 “Cotton Bowl Classic” after he recorded seven tackles, one tackle for loss, two forced fumbles, one fumble recovery, one interception, one sack, and one pass breakup.

After his college season in 2011, he was named “All-American” and he’s been a finalist for the Heisman Trophy. In 2012 he was dismissed from the LSU Tigers Football program because of a violation of team rules. The news reported that Tyrann failed repeatedly the drug tests, but the news hasn’t been confirmed. In October 2012 Tyrann has been arrested on possession of Marijuana. Tyrann entered a drug rehabilitation program in Houston, Texas, and he was drafted by the Arizona Cardinals as the 69th pick in the third round of the 2013 NFL Draft with a four-year, $3.05 million contract that included $817,187 guaranteed, and a signing bonus of $265,000.

In a statement from Cardinals' head coach Bruce Arians it has been declared that Mathieu would have been playing free safety.  Mathieu stated that he would remove himself from any association with his nickname "Honey Badger", saying that he wanted a fresh start, and to be known as "Tyrann Mathieu”.

Tyrann suffered an injury, and he received a ton of support from teammates and rivals alike. Seahawks cornerback Richard Sherman even tweeted for a speedy recovery to the Honey Badger following the season-ending knee injury his rookie year.

In 2014, he made 13 games and finished the year with a fumble recovery, four defended passes, an interception, and 39 tackles. He suffered what someone calls a “sophomore slump”. The second year defensive back finished with nearly half as many tackles as his rookie season, only one interception and no sacks or forced fumbles in the same amount of games.

In 2015, the team made Tyrann a cornerback because of the lack of the players on the team for that position. The Honey Badger enjoyed the best year of his career: not only he set a career high in tackles (80 total) and interceptions (5), but Tyrann also scored the only touchdown of his career, a 33-yard interception return against the 49ers in the third week of the season. Even the Cardinals experienced their most success as a team in the Honey Badger era in 2015. Arizona finished 13-3 to win the NFC West, and made it to the NFC Championship against the Carolina Panthers before being knocked out of the playoffs.