Seltzer became an Assistant Professor of Computer Science at Harvard University in 1992, and an Associate Professor in 1997. She held endowed chairs as a Gordon McKay Professor of Computer Science in 2000,[7] and as the Herchel Smith Professor of Computer Science in 2004. From 2005 to 2010, Seltzer was designated a Harvard College Professor in recognition of "particularly distinguished contributions to undergraduate teaching." Seltzer was the Associate Dean of the School of Engineering and Applied Sciences from 2002 to 2006, and an advisor to the Harvard Undergraduate Women in Computer Science.[8]
Seltzer co-founded Sleepycat Software (developers of the Berkeley DB embedded database) in 1996 and was the CTO until 2006, when the company was acquired by Oracle Corporation. She served as an architect on the Oracle Berkeley DB team for several years before transferring to Oracle Labs where she continues to act as an architect.
Seltzer was a director of USENIX from 2005 to 2014, serving as vice president for one year and president for two.[10] In 2019, she received the USENIX Lifetime Achievement Award for her seminal work on BerkeleyDB and provenance systems and her dedication to the USENIX community at large.[11]
In 2011, Seltzer was made a Fellow of the Association for Computing Machinery (the Association's highest member grade) in recognition of "outstanding accomplishments in computing and information technology and/or outstanding service to ACM and the larger computing community."[12][13] In July 2020, Seltzer accepted the SIGMOD Software Systems award on behalf of the Sleepycat Software team.[14]