In 1885, 6 acres (2.4 ha) were purchased in the Hyde Square section of Jamaica Plain, a residential district of Boston, to build a kindergarten, with Isabel Greeley as its first matron.

Charles Dickens visited Perkins in 1842 during a lecture tour of America and was amazed at the work Howe was doing with Laura Bridgman, a deaf-blind girl who had come to the school in 1837 from New Hampshire.

In 1887, Perkins director Michael Anagnos sent graduate Anne Sullivan to teach Helen Keller at her family's home in Alabama.

[8] Perkins has also worked with local partners in Asian countries to host an online community for educators, caregivers and families.

[13] In 2022, Perkins launched the Howe Innovation Center, dedicated to catalyzing and convening the "DisabilityTech" industry, including bringing together startups, investors, people with disabilities, and market experts.

[14] Perkins partners with local groups in 67 countries: schools, universities, NGOs, nonprofits, government agencies, and parent networks—to educate and empower people who are blind, deaf/blind or visually impaired, and who may have additional disabilities.

One such example of this work in the African countries of Tanzania, Uganda and Kenya is Perkins' role in the Kilimanjaro Blind Trust, Inc.

[18] On May 5, 2016, Perkins launched BlindNewWorld,[19] a social change campaign aimed at helping the sighted population to be more inclusive of people who are blind and to make the world more accessible to them.

[21] It aims to inform the nearly one million people in the United States with some sort of combined hearing and vision loss on the types of equipment—e.g.

[25] The international nonprofit has also worked with the American Foundation for the Blind to ensure that Expanded Core Curriculum (ECC) be taught in mainstream schools.