A major change occurred in the landscape of the neighborhood when the Erie Canal was rerouted south of downtown Rochester early in the 20^th century. The Rochester Subway, which operated from 1927-1955, was built in the old Erie Canal bed. Broad Street was constructed over the subway line.

Remains of the Erie Canal, 1910 (?)	Subway entrance on West Main, near Clarissa and Broad, dated 1938

Intersection at West Main and Broad Streets, formerly site of the Erie Canal, 1923 (?)

The Cunningham factory gained a reputation for quality luxury automobiles. Owners of Cunningham automobiles included the publisher William Randolph Hearst, storeowner Marshall Field, and actors Harold Lloyd and Mary Pickford. However, the business couldn't tap into the lucrative mass market for automobiles. It diversified into military production during World War I and later went into aircraft production. After further attempts at diversification, the company moved from Canal Street to Honeoye Falls in 1961. It later became a subdivision of Gleason Works. In 1998 St. Mary's Hospital merged with the suburban Park Ridge Hospital under the Unity Health System. St. Mary's then went from being a full-service hospital to a walk-in care center focusing on out-patient needs

Rochester City Hospital was renamed Rochester General Hospital in 1911. In 1956 it moved from the neighborhood to a location on Portland Avenue.

Pennsylvania Station was razed in 1933. Nick Tahou converted the Buffalo, Rochester & Pittsburgh station into a restaurant in 1963.

The old Saints Peter and Paul Church was torn down circa 1910 and a new church was built on West Main Street.

Problems which affected practically all urban areas in the 1950's and 1960's contributed to a decline in the West Avenue neighborhood as well.