Selected in the first round (19th overall) out of California in the 1997 NFL Draft, Tarik Glenn stepped into the Indianapolis Colts' starting lineup as a rookie at right guard before permanently locking down the crown-jewel spot at left tackle. Possessing rare functional strength and light-footed agility, Glenn anchored the blind side of the offensive line for a decade, serving as the trusted primary protector for Peyton Manning during the franchise's meteoric rise to elite status.

Glenn’s presence was the rock around which offensive line coach Howard Mudd built one of the most efficient pass-blocking units in gridiron history. Tasked with shutting down the league's most terrifying edge rushers without assistance, Glenn’s mastery at left tackle allowed Manning's high-octane, no-huddle offense to flourish without fear of backside pressure. He started all 16 games in seven of his 10 professional seasons, earning three consecutive Pro Bowl selections from 2004 through 2006 as national recognition caught up to his elite on-field production.

His career reached a fairytale climax during the 2006 campaign. After dominating through four postseason victories, Glenn’s final game in uniform came on football's grandest stage, Super Bowl XLI. On a rain-soaked field in Miami, Glenn neutralized the Chicago Bears' pass rush, helping clear the way for 425 total yards of offense in a 29–17 victory. Walking off the field as a world champion, Glenn announced his retirement that offseason at the top of his game. He was permanently enshrined in franchise lore when he was inducted into the Indianapolis Colts Ring of Honor in 2022.

Glenn notably started all 154 games of his career.