^ According to Mary E. Chayer of Teacher's College, Columbia University, an unverified report gave Mary Eliza Mahoney's birth date as April 16, 1845 in Roxbury. Other sources list her date of birth as May 7, 1845.

Mahoney knew early on that she wanted to become a nurse; possibly due to seeing immediate emergence of Nurses during the American Civil War. She was admitted into a 16-month program at the New England Hospital for Women and Children (now the Dimock Community Health Center) at the age of 33, alongside 39 other students in 1878. The NEHWC became the first institution to offer such a program allowing women to work towards entering the Health care industry, which was predominantly led by men. The criteria in which the hospital utilized while choosing students for their program emphasized that the 40 applicants would be "well and strong, between the ages of 21 and 31, and have a good reputation as to character and disposition." It is presumed that the administration accepted Mahoney, despite not meeting the age criteria, because of her connection to the hospital through prior work as a cook, maid, and washerwoman there when she was 18 years old. Mahoney worked nearly 16 hours daily for the 15 years that she worked as a laborer.

Mahoney's training required she spend at least one year in the hospital's various wards to gain universal nursing knowledge. The work within the program was intensive and consisted of long days with a 5:30 A.M. to 9:30 P.M. shift, requiring Mahoney to attend lectures and lessons to educate herself through instruction of doctors in the ward. Outside of the lectures, students were taught many important bedside procedures such as taking vital signs and bandaging. In addition, Mahoney worked for several months as a private-duty nurse. The nursing program allowed for the students to earn a weekly wage, ranging from 1 to 4 dollars, after their first two weeks of work. Many Nurses did not see the weekly wages as significant as many of them were struggling financially and thus were giving back 25% of their wages for financial assistance to the hospital. Three quarters of the program consisted of the Nurses working within a surgical, maternity or medical ward with six patients they were responsible caring for. The last two months of the extensive 16-month long program required the Nurses to use their newfound knowledge and skills in environments they were not accustomed to; such as hospitals or private family homes. After completing these requirements, Mahoney graduated in 1879 as a registered nurse alongside 3 other colleagues — the first black woman to do so in the United States.

In 1896, Mahoney became one of the original members of a predominantly white Nurses Associated Alumnae of the United States and Canada (NAAUSC), which later became the American Nurses Association (ANA). In the early 1900s, the NAAUSC didn't welcome African-American Nurses into their association. In response, Mahoney founded a new, more welcoming nurse's association, with help of other founders, one being Martha Minerva Franklin. In 1908, she became co-founder of the National Association of Colored Graduate Nurses (NACGN). This association didn't discriminate against anyone and aimed to support and congratulate the accomplishments of all outstanding Nurses, and to eliminate racial discrimination in the nursing community. The association also strived to commemorate minority Nurses on their accomplishments in the registered nursing field. In 1909, Mahoney spoke at the NACGN's first annual convention, which became the first time that Martha Minerva Franklin and Adah Belle Samuels Thoms met Mahoney in person. The NACGN struggled in their early stages with only 26 female Nurses in attendance of their first national convention. In her speech, she recognized the inequalities in her nursing education, and in nursing education of the day. The NACGN members gave Mahoney a lifetime membership in the association and a position as the organization's chaplain.

In 1908, Mahoney co-founded the National Association of Colored Graduate Nurses (NACGN) with Adah B. Thoms. This organization attempted to uplift the standards and everyday lives of African-American registered Nurses. The NACGN had a significant influence on eliminating racial discrimination in the registered nursing profession. In 1951, the NACGN merged with the American Nurses Association.

From 1911 to 1912, Mahoney served as Director of the Howard Orphan Asylum for black children in Kings Park, Long Island, New York. The Howard Orphan Asylum served as a home for freed colored children and the colored elderly. This institution was run by African Americans. Here, Mary Eliza Mahoney finished her career, helping people and using her knowledge however she knew best.

In retirement, Mahoney was still concerned with women's equality and a strong supporter of women's suffrage. She actively participated in the advancement of civil rights in the United States. In 1920, after women's suffrage was achieved in the U.S., Mahoney was among the first women in Boston to register to vote.

In 1923, Mahoney was diagnosed for breast cancer and battled the illness for 3 years until she died on January 4, 1926, at the age of 80. Her grave is located in Woodlawn Cemetery in Everett, Massachusetts. In 1968 Helen Sullivan Miller, a recipient of the Mary E. Mahoney Medal, spearheaded a drive to establish a proper monument.

In recognition of her outstanding Example to Nurses of all races, the NACGN established the Mary Mahoney Award in 1936. When NACGN merged with the American Nurses Association in 1951, the award was continued. Today, the Mary Mahoney Award is bestowed biennially by the ANA in recognition of significant contributions in advancing equal opportunities in nursing for members of minority groups.

Mahoney was inducted into the ANA's Hall of Fame in 1976. She was inducted into the National Women's Hall of Fame in 1993.