As a true freshman at the University of Miami in 2012, Flowers played in all 12 games at right tackle, making four starts.[6][7] As a sophomore in 2013, he started all 12 games at left tackle.[8] He returned as the starting left tackle in 2014. On December 29, 2014, Flowers announced that he would forgo his senior season and enter the 2015 NFL draft.[9]
On April 30, 2015, Flowers was selected with the ninth overall pick by the New York Giants in the 2015 NFL Draft.[12] He was the highest selected Miami Hurricanes offensive lineman since Bryant McKinnie in 2002. On June 18, 2015, Flowers signed a 4-year $14.3 million contract with the Giants. He was named the Giants starting left tackle for Week 1 and played in 15 games in his rookie season.
Although he wore number 76 jersey throughout his entire rookie season, Flowers decided to switch to his college number 74 during the spring of 2016 after it was left available with the departure of teammate Geoff Schwartz.
Flowers has been criticized for not living up to expectations through his 3rd year in the league. Since 2015, he gave up 169 total pressures which is the most of any tackle in the NFL during that time.[13] Those stats and his numerous penalties have caused Pro Football Focus to rate him as the 54th best tackle in the NFL.[14] In 2018, former offensive line teammate and NFL analyst Geoff Schwartz accused Flowers of "quitting" on the team, of missing multiple blocks, and of having poor technique.[15][16]
On May 2, 2018, the Giants declined the fifth-year option on Flowers’ contract, making him a free agent in 2019.[17] He was moved over to right tackle after the Giants signed veteran Nate Solder to be their left tackle. On September 23, 2018, the Giants decided to bench Flowers in favor of Chad Wheeler at right tackle after his continued struggles.[18] On October 8, 2018, the Giants announced plans to release Flowers if a trade with a team couldn't be worked out. The next day, Flowers was officially released by the Giants.[19]
On October 12, 2018, the Jacksonville Jaguars signed Flowers to a one-year contract after Josh Wells was placed on injured reserve.[20] He was named the starting left tackle in Week 11 and started there the rest of the season.
On March 20, 2020, Flowers signed a three-year, $30 million contract with the Miami Dolphins.[23][24][25] He was placed on the COVID-19 reserve list by the team on August 2, 2020, before being activated on August 15.[26]
On April 28, 2021, Flowers was traded to the Washington Football Team in exchange for a swap of 2021 seventh round picks from both teams.[27][28] On December 31, 2021, he was placed on the team's COVID-19 reserve list and was forced to sit out of the Week 17 game against the Philadelphia Eagles.[29] Flowers was placed back on active roster on January 5, 2022.[30] Flowers was released on March 16, 2022.[31]