Bruce Smith attended Virginia Tech and was drafted by the Buffalo Bills as the number one draft pick overall in the 1985 NFL Draft. Smith became known as a sack specialist, with 15 in 1986 and a personal season-best 19 in 1990. By 1989, Smith had already become the Bills' all-time sack leader when he reached his 52nd sack. In 1990, his defensive performance helped bring the Bills to Super Bowl XXV, but they eventually lost to the Bill Parcells-led New York Giants. Still Smith had an impressive performance in the game. He sacked Jeff Hostetler in the end zone for a safety in the second quarter, and later forced New York to turn the ball over on downs by tackling running back Ottis Anderson for a 2-yard loss on a fourth down conversion attempt.

At the height of his career Smith was known as one of the NFL's most fearsome defensive players, his sack record attests to this, though his public demeanor suggested he was quite mild-mannered off the field.

In 1991, Smith was hampered by knee problems and sat out most of the season. And while Smith would continue to be productive for many more seasons, it was ongoing knee troubles that eventually led to his decline several seasons later.

During these years, Smith continued to be named to the Pro Bowl every season from 1987 to 1998 (except for his injury-laden 1991 season). In 1987, he was named the Pro Bowl MVP. Smith was twice named the AP's NFL Defensive Player of the Year (1990, 1996) and thrice named UPI's AFC Defensive Player of the Year (1988, 1990, 1996).

By 1996, Smith was still putting up prolific numbers, with 90 tackles and 14 sacks, but his performance began to decline. By 1997, Smith had 65 tackles and 14 sacks and by 1998, he had a still-respectable 50 tackles and 10 sacks, but his days of huge numbers had passed.

After the 1999 season, Smith signed with the Washington Redskins as a free agent. In his first season, he posted 58 tackles and 10 sacks, but his production waned and he became limited to only a handful of downs per game. He pressed onward, however, in pursuit of Reggie White's all-time sacks record (198), which he finally passed in the thirteenth game of his nineteenth season in 2003. Smith finished the season with 200 career sacks.

Smith had hinted in interviews that 2003 would be his final season. However, he never completely ruled out continuing to play. But on February 24, 2004, the Redskins released Smith, saving $6.5 million in salary cap space.

In his 19 NFL seasons, Smith played in 279 games, amassing 200 sacks, 2 interceptions, 33 forced fumbles, and 15 fumble recoveries, which he returned for 33 yards and a touchdown. Also, of his 20 seasons in the NFL, 14 of them were seasons where he had at least 10 sacks, a testament to his consistency year and year out.

In 2006, Bruce was voted into the College Football Hall of Fame.