The Bills' 1–12–1 record in 1968 (a 0.107 winning percentage) is the second-worst in team history: the 1971 Bills went 1–13. They were one of only two teams in AFL history (the other being the 1962 Oakland Raiders) to finish the season with only one victory.
The Bills, coming off a 4–10 season in 1967, fired coach Joe Collier after an 0–2 start in 1968. Defensive backfield coach Harvey Johnson was promoted to interim head coach, where he went 1–10–1 to finish the year.
The majority of Buffalo's games were started by backup quarterback Dan Darragh, after injuries claimed the seasons of long-time starter Jack Kemp and new addition Tom Flores. Even Darragh and new addition Kay Stephenson were injured. Ultimately, running back Ed Rutkowski, who hadn't played the quarterback position since college six years prior, ended up starting at quarterback for the Bills.
Buffalo's only win of the season was a home victory over the New York Jets, in which the Bills held a 16-point lead in the fourth quarter before giving up two late touchdowns to the Jets. Ultimately, the Bills were able to hold on to the two-point win.