She moved to California State University, Northridge in 1977 as administrative coordinator of its NEH Liberal Studies Project.

From 1978 to 1979, she was acting director of California State University, Northridge's International Programs and visiting associate professor of Pan-African Studies.

[17] In November 2000, Simmons was named as the first African-American woman to head an Ivy League school.

As reported in a May 22, 2009 press release, Brown Chancellor Thomas J. Tisch announced the early attainment of the $1.6 billion fundraising campaign and the continued pursuit of specific subsidiary goals in support of endowments for student scholarships of the Brown faculty and internationalization programs through the originally planned campaign to be continued through December 31, 2010.

Nevertheless, a 2007 New York Times article, featuring a photograph of Simmons, reported that the Harvard Corporation, responsible for selecting the university's replacement for former president Lawrence Summers, had been given a list of "potential candidates" that included her name.

"[28] Simmons was cited in the 2010 film Inside Job, as an example of the conflicts of interest between university economics departments and deregulation of financial institutions.

[31][32][33] On February 16, 2007, at an event celebrating the 200th anniversary of the passage of the Slave Trade Act 1807 and the involvement of Cambridge University alumni William Wilberforce, Thomas Clarkson and William Pitt the Younger, Simmons delivered a lecture at St. John's College, Cambridge, entitled Hidden in Plain Sight: Slavery and Justice in Rhode Island.

[35] In October 2007, Simmons appointed David W. Kennedy, as vice president for international affairs.

[38][39] On September 15, 2011, Simmons announced that she would retire from the Brown presidency at the end of the academic year, June 30, 2012.

[40] In 2017, after five years of retirement, Simmons accepted an offer to serve as the interim president of Prairie View A&M University, an HBCU in her home state of Texas.

[42][43] At Prairie View A&M, Simmons focused her efforts on improving the university's financial stability, particularly on fundraising through an anonymous donor for the Panther Success Grants for undergraduates.

[2] In 2022, Prairie View A&M announced that scholarships had increased and donations to the university had grown by 40% during Simmons’ 5-year presidency.