List of Buffalo Bills first-round draft picks

The Buffalo Bills are a professional American football team based in the Buffalo–Niagara Falls metropolitan area. The Bills compete in the National Football League (NFL) as a member of the East Division of the American Football Conference. Founded in 1959 by Ralph Wilson, they were a charter member of the American Football League (AFL) and joined the NFL in 1970 following the AFL–NFL merger. The Bills' name is derived from an All-America Football Conference franchise from Buffalo that was in turn named after western frontiersman Buffalo Bill. Since 1973 they have played their home games at Highmark Stadium in Orchard Park, New York.

The NFL draft, officially known as the "NFL Annual Player Selection Meeting",  is an annual event which serves as the league's most common source of player recruitment. The draft order is determined based on the previous season's standings; the teams with the worst win–loss records receive the earliest picks. Teams that qualified for the NFL playoffs select after non-qualifiers, and their order depends on how far they advanced, using their regular season record as a tie-breaker. The final two selections in the first round are reserved for the Super Bowl runner-up and champion. Draft picks are tradable and players or other picks can be acquired with them.

Before the merger agreements in 1966, the AFL directly competed with the NFL and held a separate draft. This led to a bidding war over top prospects between the two leagues, along with the subsequent drafting of the same player in each draft. As part of the merger agreement on June 8, 1966, the two leagues began holding a multiple round "common draft". Once the AFL officially merged with the NFL in 1970, the "common draft" simply became the NFL draft. The first AFL draft was held prior to the start of the 1960 season. The first round of the 1960 AFL draft was territorial selections. Each team received a "territorial pick" which allowed them to select a single player within a pre-agreed upon designated region (the team's "territory"). Teams then agreed on the top eight players at each position, who were subsequently assigned to teams by random draw, with each of the eight teams receiving one of those players. This process was repeated until all 53 roster spots were filled. Beginning in the 1961 draft, the AFL, using the same system as the NFL, began to assign picks based on the previous season's standings.

Since the team's first draft, the Bills have selected 67 players in the first round. The team's first-round pick in the inaugural AFL draft was Richie Lucas, a quarterback out of Penn State; he was the team's territorial selection. The Bills have held the first overall pick five times, four times in the NFL draft and once in the AFL draft. They selected Ken Rice in 1961, O. J. Simpson in 1969, Walt Patulski in 1972, Tom Cousineau in 1979, and Bruce Smith in 1985. In the most recent draft, held in 2024, the Bills did not draft a player in the first round.

The Bills did not draft a player in the first round on seven occasions. Five of the team's first-round picks—Joe DeLamielleure, Carl Eller, Jim Kelly, O. J. Simpson, and Bruce Smith—have been elected to the Pro Football Hall of Fame; one of these, Carl Eller, chose not to play for the Bills and joined the NFL instead. The Bills used an additional two first-round picks in the 1960s to select players—Ernie Davis and Mike Dennis—who also chose to sign with the NFL instead.