While suitable for AFL play in the 1960s, the "Rockpile" (as the stadium came to be nicknamed), was in disrepair and with a capacity of under 47,000, undersized for a National Football League (NFL) team.

In early 1971, owner Ralph Wilson was exploring options to relocate the team, possibly to Seattle,[7][8][9] with other cities such as Memphis and Tampa soon expressing interest as well.

Rich Products balked at paying a greatly increased rights fee,[26] which would have brought the price up to par with other NFL stadiums.

On August 13, 2016, Buffalo-based New Era Cap Company and the Bills reached a seven-year, $35 million agreement for stadium naming rights.

[29] On July 15, 2020, the Bills announced that New Era Cap asked to be released from their naming rights and sponsorship deal, and the two sides agreed on terms to terminate the contract.

In 1994, major renovations were made to the stadium including the addition of the Red Zone and Goal Line clubs that are enclosed in glass and have 500 seats.

A massive $9.1 million (inflation adjusted) 41.5 by 31.5 feet (12.6 by 9.6 m) Sony JumboTron video scoreboard was a major update in 1994 and was the largest in the U.S. at the time.

The lease agreement also stipulated Erie County would continue to upgrade the stadium; in the summer of 2007, a new HD Mitsubishi LED board measuring 88.8 by 32.5 feet (27.1 by 9.9 m) was installed and replaced the 13-year-old Sony Jumbotron.

The total cost for the 2007 project was $5.2 million, In 2011, the Bills changed their turf to a new product, A-Turf Titan, produced by a Western New York company.

[39] Buffalo, by virtue of its position downwind of Lake Erie, is one of the nation's windiest cities, and as a result, Highmark Stadium is difficult for kickers, with swirling winds that change direction rapidly.

The size of the field at Highmark Stadium is specifically designed for National Football League dimensions and sight lines, along with football and team markings being formed permanently into the turf, making it extremely difficult for other outdoor sporting events such as soccer, baseball, track and field, or rugby to be held there.

The stadium annually hosts the region's Section VI and Monsignor Martin Athletic Association high school football playoffs.

The Grateful Dead played the stadium a 5 times including 7/4/86, 7/4/89, 7/16/90, 6/6/92, and 6/13/93 with their July 4, 1989 Truckin' Up to Buffalo performance being documented on Vinyl, CD, and DVD.

A Bruce Springsteen concert, that was originally scheduled at the stadium in 2003, was moved to the smaller Darien Lake Performing Arts Center due to low ticket sales.

This was due to the combination of a declining number of stadium rock acts, population decline, and the availability of other, more intimate, venues in Western New York such as Artpark in Lewiston, Darien Lake Performing Arts Center in Corfu, the Thursday at the Square series among others, Seneca Niagara Casino, and the KeyBank Center, which opened in 1996, replacing Buffalo Memorial Auditorium in downtown Buffalo.

During his press conference to acquire the team, Terry Pegula stated, "we will gradually proceed to plan and design a stadium for the Buffalo Bills.

"[68] On June 18, 2021, the Pegulas chose Legends Global Planning to represent ownership, consult on a new stadium and sell sponsorships and premium seats for the venue.

It will be built across the street from Highmark Stadium adjacent to Erie Community College’s south campus, and is expected to open in 2026.

[72] Since the Bills moved from War Memorial Stadium into their current home, it has been noted that the team has not won a championship since, and has had frequent periods of heartbreak, including four Super Bowl losses in a row.