Drafted in the second round (32nd overall) of the 1979 NFL Draft out of Boston College, Fred Smerlas arrived in Western New York as a relentless, physical force. Tipping the scales at 6 feet 3 inches and 275 pounds, he redefined nose tackle play in Chuck Knox’s 3-4 defense, anchoring the center of Buffalo's front line during an era of massive franchise transition.

Smerlas operated with a low center of gravity, aggressive hand techniques, and relentless energy. Positioned centrally, he excelled at breaking double-teams and absorbing hits in the interior, enabling linebackers like Shane Conlan and Darryl Talley to make tackles. Unlike typical nose tackles of his time, Smerlas was noteworthy for his lateral agility—he often shed blocks to disrupt running lanes or collapse the pocket during passing plays.

Smerlas became the starting nose tackle full-time in 1980 during his sophomore year, earning his first Pro Bowl selection as he led a defense that helped Buffalo win its first AFC East title in four years. He reaffirmed his status in 1981 with another Pro Bowl appearance, cementing his reputation as one of the top interior defensive linemen in the league.

His peak performance came in the limited 1982 season. As the key threat on a defense that helped Buffalo stay competitive, Smerlas had a standout run that earned him his only First-Team All-Pro honor and his third straight Pro Bowl selection.

Despite the Bills experiencing several tough losing seasons in the mid-1980s, Smerlas remained a fan favorite and a standout player in Western New York. He earned two more Pro Bowl selections in 1983 and 1988, playing a key role on the defense as young stars like Bruce Smith, Cornelius Bennett, and Jim Kelly helped turn Buffalo into a powerhouse. By the late 1980s, Smerlas's efforts paid off as the team became a consistent contender, winning back-to-back AFC East titles in 1988 and 1989.

After 11 seasons in Buffalo, Smerlas departed after the 1989 campaign as the Bills transitioned to younger defensive linemen. He played one season for San Francisco in 1990 and finished his career with New England in 1991 before retiring.

With the Bills, Smerlas played in 162 regular-season games, accumulating 29 official sacks and recovering 11 fumbles. In recognition of his stellar play and lasting popularity, Smerlas was inducted into the Buffalo Bills Wall of Fame in 2001.