Taken in the second round (29th overall) of the 1987 NFL Draft out of Wisconsin, Nate Odomes stepped directly into the Buffalo secondary and became a key defensive pillar throughout the franchise's legendary run of four straight AFC Championships. Functioning as a ball-hawking shutdown cornerback on the outside, Odomes possessed the rare instincts and closing speed that routinely turned defensive stops into game-changing turnovers.

Odomes integrated physical press coverage at the line of scrimmage with outstanding ball-tracking abilities in deep zone schemes. When defending against the opponent's best wideouts, he employed quick, fluid hips and an aggressive recovery burst to break up route stems. His defining trait was his diagnostic vision: Odomes immediately recognized quarterback eye progression, jumping intermediate passing lanes to turn precise throws into quick interceptions.

Odomes has a talent for making crucial plays in high-pressure postseason moments. In the notable 1992 AFC Wild Card Game—"The Comeback"—he made a decisive interception of Oilers quarterback Warren Moon, which led to the game-winning field goal and marked the greatest comeback in playoff history. He maintained his reputation for clutch performance by intercepting passes in both Super Bowl XXVII and Super Bowl XXVIII.

His individual performance peaked during his 1993 campaign. Odomes co-led the NFL with a career-high nine interceptions, spearheading Buffalo's pass defense and earning his second consecutive Pro Bowl selection and Second-Team All-Pro honors.

During his seven seasons with the Bills (1987–1993), Odomes started 107 regular-season games, recording 26 interceptions, eight fumble recoveries, and two defensive touchdowns. He signed with the Seattle Seahawks as a free agent in 1994, but severe knee injuries kept him out for two seasons. He made a brief comeback with Atlanta in 1996. Odomes's significant impact was honored when he was named to the Buffalo Bills 50th Anniversary Team.