Kelly Gregg was selected in the sixth round of the 1999 NFL Draft by Cincinnati but was released before playing any regular-season games in Ohio. After brief stints with Philadelphia and on Baltimore's practice squad, he proved his resilience by competing in NFL Europe with the Rhein Fire, eventually becoming a regular in Maryland. At 6 feet tall and 320 pounds, Gregg didn’t have long limbs, but he compensated with wrestling leverage, toughness, and relentless energy as a nose tackle.

Gregg was the quintessential gritty interior lineman. Positioned directly over the center, his low center of gravity made him nearly immovable by single blocks. In Baltimore's 3-4 system, his primary role was to handle double-teams from guards and centers, taking the hits so linebackers like Ray Lewis and Terrell Suggs could attack the ball. Despite facing double-teams on almost every snap, Gregg had the lateral quickness to disengage and make tackles in the run gap.

Gregg joined the Ravens' practice squad during their landmark 2000 season and earned a Super Bowl XXXV ring behind the scenes. He made his first rotational appearance in 2001 and became the full-time starting nose tackle in 2002. That breakout year, he recorded 56 total tackles and two sacks, demonstrating he could lead a defense on his own terms.

His best statistical season came in 2003, when he recorded 80 total tackles and 3.0 sacks—unusually high production for a 0-technique nose tackle. Year in and year out, Gregg served as the silent engine of run defenses that routinely ranked near the top of the NFL. In 2007, he posted a career-high 83 total tackles while starting all 16 games.

Though he never earned Pro Bowl recognition—a common fate for non-flashy interior nose tackles—Gregg earned immense respect across the locker room and throughout the league for his durability and toughness. After missing 2008 due to microfracture knee surgery, he returned to start every game in 2009 and 2010, anchoring Baltimore's front five through his age-34 season.

Salary-cap constraints resulted in his release in July 2011, along with veteran teammates Todd Heap and Derrick Mason. He concluded his career with a single season in Kansas City. During his decade with Baltimore (2001–2010), Gregg appeared in 134 regular-season games, starting 124, and recorded 512 tackles, 19.5 sacks, and two forced fumbles.