He eventually purchased several manufacturing outlets, construction firms, television and radio stations, and founded Ralph Wilson Industries.

Wilson made professional football a resounding success in a "small market", signing such stars as Cookie Gilchrist, Jack Kemp, and Tom Sestak and Hall of Famers Billy Shaw and O. J. Simpson.

"[11] In 1989, after league commissioner Pete Rozelle announced his retirement, Wilson was on the six-member committee who was tasked with nominating potential candidates for the open position.

[13] He publicly rebuked NFL Commissioner Paul Tagliabue in an open letter in 1998 over league policy, which disallowed criticism of referees, after poor officiating had a direct impact on a Bills loss that season.

Wilson maintained a permanent residence in Grosse Pointe Shores, Michigan with his wife, Mary McLean, whom he met in 1989.

The highest ranking relative in the organization was Mary Owen, Wilson's niece, who served as Vice President of Strategic Planning until the team was sold.

He was hospitalized in August and early September 2012 with an unspecified infection and missed attending games in the entire 2012 season.

[26] His estate held the franchise in trust until its sale to Buffalo Sabres owners Terry and Kim Pegula in September 2014.

[30] On January 31, 2009, Wilson was elected to the Pro Football Hall of Fame along with former Buffalo Bills defensive end Bruce Smith.

[31] The Hall of Fame game, played the day after the 2009 inductions, strayed from the usual AFC–NFC format and instead was contested by two original American Football League teams: the Buffalo Bills and the Tennessee Titans (formerly the Houston Oilers).

Wilson was officially inducted into the Pro Football Hall of Fame on Saturday, August 8, 2009, with ESPN icon Chris Berman acting as his "presenter".

[33] Wilson was scheduled to receive his Hall of Fame ring in a halftime ceremony during the Bills game against the Cleveland Browns on October 11, 2009.

It was widely speculated that Wilson cancelled the event out of fear of being booed by Bills fans for the team's chronic poor performance on the field and a series of highly unpopular managerial decisions.

[35] Wilson was also involved for a number of years in the sport of Thoroughbred horse racing both as a breeder and as an owner in France and the United States.