Wrighton moved with his family from Jacksonville to Virginia, Tennessee, Maryland, and Newfoundland, and he went to high school in Pensacola, Florida.

Jack Saltiel[6] became his advisor and mentor, and he continued undergraduate research in the area of organic photochemistry.

[8] Wrighton joined the faculty of the chemistry department at the Massachusetts Institute of Technology in the summer of 1972 as an assistant professor.

"[9] Wrighton's research interests are centered on photochemistry and transition metal catalysis, and include surface chemistry, molecular electronics and photoprocesses at electrodes.

[10] Wrighton has carried out work in the areas of inorganic photochemistry, photocatalysis and the use of solar energy in photovoltaics.

[12][13] Wrighton was one of the first researchers to introduce the idea of electrochemical gating as a way of controlling charge transport in molecular electronics.

Major programmatic initiatives during Wrighton's chancellorship include: the McDonnell International Scholars Academy; the Alvin J. Siteman Cancer Center; the Gephardt Institute for Civic and Community Engagement; the Institute for Public Health; the International Center for Energy, Environment and Sustainability; and the Living Earth Collaborative.

Wrighton distanced himself from the board's decision with a letter to the community disavowing Schlafly's views on science.

[25] In February 2022, Wrighton caused controversy after removing posters from campus that accused the Chinese government of human rights abuses and criticized the country's hosting of the 2022 Winter Olympics.

[27] Wrighton clarified in a public message that after his initial comments he learned the posters were designed by a Chinese-Australian artist and were a critique of China’s policies.

He served as vice chair of the National Research Council's Committee on America's Energy Future, which issued its report in 2009.