Spain signed with the Tennessee Titans as an undrafted free agent following the 2015 NFL Draft. He made the Titans final roster as a rookie, playing in seven games with six starts at guard. In 2016, Spain won the starting left guard spot and started 13 games, missing 3 due to injury. The 2016 Titans offensive line was heralded as one of the best in the league.
Spain started the 2017 season as the Titans' starting left guard.