Born in Clintonville, New York, Brush was orphaned at four years old and was raised by his grandfather until he left to enter business college at age 17.

When the National League (NL) put the St. Louis Maroons franchise up for sale after the 1886 season, Brush bought it and relocated the team to Indianapolis.

Brush renovated his ballpark, adding a special celebrity box which attracted such figures as President Benjamin Harrison, poet James Whitcomb Riley, and future novelist Booth Tarkington.

[6] When the Giants won the 1904 NL pennant, Brush refused to allow the team to meet Boston's defending champions (then known as the Boston Americans) in a 1904 World Series, due to his animosity toward Johnson; a permanent agreement between the leagues was eventually made after meeting some of Brush's conditions, and the Giants won the 1905 World Series against the Philadelphia Athletics.

The Giants were again defeated, and his failing health was apparent, particularly in the aftermath of an auto accident that September 11 in which his car was struck by a truck and overturned,[7] causing two broken ribs.

After the Series he left by train to recuperate in California, but died in the early hours of November 26 in his private railroad car near Louisiana, Missouri.

In 1913, the Giants organization constructed a stairway from the ticket booths on Coogan's Bluff to the Polo Grounds below, and presented it to the City of New York in honor of its late owner.