William J Mayo was the older of the two Mayo brothers who, along with five partners, founded the not-for-profit Mayo Clinic in Rochester. William was the more serious of the two brothers and was often described in one word — brilliant. William married Hattie Damon in 1884. Together, they set out to build a new home. They found a large lot with a number of mature trees that they both loved at 427 West College Street. There was already a modest home on the property that needed to be demolished before they could build their dream home. Their new Queen Anne style home was completed in 1888. A broad porch graced the front with a gazebo at the corner. The exterior was painted conservatively–pale yellow with white trim–and the home featured modern conveniences such as gas lights and running water. 
William and Charles spent most of their lives together, so after William married and moved from their parent’s house, he offered Charles a room at his new home. Charles continued to live with William and his family until he married and built his own house next door to William. 

Charles was the more outgoing and sociable of the two brothers. Even his home at 419 West College Street showed his personality — it was painted a warm red color that stood out in the neighborhood. After living at William’s home for a few years, Charles’ upcoming wedding spurred him to purchase the lot next door to his brother and build a new home for his bride. Construction began in the months following the wedding in April 1893 to a nurse-anesthetist, Edith Graham. Completed in 1894, the Queen Anne style home featured a turreted tower which flanked a second-floor porch that overlooked the street below. The three-story home’s main level sat high above the street due to its raised basement, making the home appear larger than it was.

When Charles and Edith moved into Mayowood in 1910 the couple donated their home on College Street to the YMCA to use as their headquarters. Through the years the house went on to become a residence for nurses, and then a privately owned rooming house for clinic visitors. In 1980, the home was placed on the National Register of Historic Places even though the original exterior had been covered with white aluminum siding and the trim was painted in several garish colors. In 1987, the homes last owners, Rosie and Rex Savage, sold the land to the Mayo Clinic on the condition that the Savage’s would demolish the house before the purchase was final. They quickly complied but failed to obtain the demolition permit required by the state for razing a property on the National Register, and were charged with a misdemeanor. A parking lot occupied the site for several decades. When Charles and his wife moved away from College Street, William and Hattie moved as well. They sold their property to Kahler Corporation who demolished it in 1918 to make way for a building of luxury rentals. 

It is often mistakenly reported that the Mayo brother’s properties on College Street featured an underground tunnel between the two homes. In fact, it was proposed but neither Charles or William’s wives liked the idea and struck it from the plans. Instead, an underground voice tube—similar to those used on ships of the era—was installed so that they could talk easily. It was especially handy since they always rode to work together—they would use the voice tube to let the other know when they were ready to leave and meet at the carriage house that was located behind the homes.