Sambrailo was selected by the Denver Broncos in the second round, 59th overall, in the 2015 NFL draft.[6] He opened the first three games of the season at left tackle before being placed on injured reserve with a shoulder injury on November 2, 2015.[7] On February 7, 2016, Sambrailo was part of the Broncos team that won Super Bowl 50. In the game, the Broncos defeated the Carolina Panthers by a score of 24–10.[8]
Atlanta Falcons
On September 1, 2017, Sambrailo was traded to the Atlanta Falcons in exchange for a 2018 fifth round draft pick.[9] He played in 15 games for the Falcons in 2017, starting two at right tackle in place of the injured Ryan Schraeder.[10]
In 2018, Sambrailo played in all 16 games, starting three at right tackle and one at left guard.[11]
On February 19, 2019, Sambrailo signed a three-year contract extension with the Falcons.[12] After splitting reps with rookie Kaleb McGary at right tackle in Week 1, Sambrailo was named a backup tackle.[13] On December 29, 2019, Sambrailo caught his first career touchdown from Matt Ryan against the Tampa Bay Buccaneers.[14]
The Falcons released Sambrailo on March 16, 2020.[15]
Tennessee Titans
On March 25, 2020, Sambrailo signed with the Tennessee Titans.[16] After entering the 2020 season as the Titans swing tackle, he was named the starting left tackle in Week 7 after an injury to Taylor Lewan. He was placed on injured reserve on November 24, 2020.[17]
Sambrailo re-signed with the Titans on March 22, 2021.[18]
On October 12, 2021, Sambrailo announced his retirement.[19]