The Bills' uniforms in its first two seasons were based on those of the Detroit Lions at the time. The team's original colors were Honolulu blue, silver and white, and the helmets were silver with no striping. There was no logo on the helmet, which displayed the players' numbers on each side.
In 1962, the standing red bison was designated as the logo and took its place on a white helmet. In 1962, the team's colors also changed to red, white, and blue. The team switched to blue jerseys with red and white "LSU" stripes on the shoulders. the helmets were white with a red center stripe. The jerseys again saw a change in 1964 when the shoulder stripes were replaced by a distinctive stripe pattern on the sleeves consisting of four stripes, two thicker inner stripes and two thinner outer stripes all bordered by red piping. By 1965, red and blue center stripes were put on the helmets.
The Bills introduced blue pants worn with the white jerseys in 1973, the last year of the standing buffalo helmet. The blue pants remained through 1985. The face mask on the helmet was blue from 1974 through 1986 before changing to white.
The standing bison logo was replaced by a blue charging one with a red slanting stripe streaming from its horn. The newer emblem, which is still the primary one used by the franchise, was designed by aerospace designer Stevens Wright in 1974.
In 1984, the helmet's background color was changed from white to red, primarily to help Bills quarterback Joe Ferguson distinguish them more readily from three of their division rivals at that time, the Baltimore Colts, the Miami Dolphins, and the New England Patriots, who all also wore white helmets at that point. Ferguson said "Everyone we played had white helmets at that time. Our new head coach Kay Stephenson just wanted to get more of a contrast on the field that may help spot a receiver down the field." (The Patriots now use a silver helmet, the Colts have since been realigned to the AFC South, and the New York Jets, who switched to green helmets after the 1977 season, have since switched back to white helmets.)
In 2002, under the direction of general manager Tom Donahoe, the Bills' uniforms went through radical changes. A darker shade of blue was introduced as the main jersey color, and nickel gray was introduced as an accent color. Both the blue and white jerseys featured red side panels. The white jerseys included a dark blue shoulder yoke and royal blue numbers. The helmet remained primarily red with one navy blue, two nickel, two royal blue, two white stripes, and white face mask. A new logo, a stylized "B" consisting of two bullets and a more detailed buffalo head on top, was proposed and had been released (it can be seen on a few baseball caps that were released for sale), but fan backlash led to the team retaining the running bison logo. The helmet logo adopted in 1974—a charging royal blue bison, with a red streak, white horn and eyeball—remained unchanged.
In 2005, the Bills revived the standing bison helmet and uniform of the mid-1960s as a throwback uniform.
The Bills usually wore the all-blue combination at home and the all-white combination on the road when not wearing the throwback uniforms. They stopped wearing blue-on-white after 2006, while the white-on-blue was not worn after 2007.
For the 2011 season, the Bills unveiled a new uniform design, an updated rendition of the 1975–83 design. This change includes a return to the white helmets with "charging buffalo" logo, and a return to royal blue instead of navy.