Patterson's early career involved diverse roles like website design, technical writing, teaching math, and restaurant criticism for the Houston Press.

She introduced innovative techniques to counter SQL injection attacks and integrated data mining libraries into PostgreSQL databases, giving rise to her startup, Osogato.

[12] Patterson has contributed to multiple open-source database software projects, including SciTools,[13] Klein,[14] and QBE,[15] and written patches to PostgreSQL.

In 2009 at BlackHat, Dan Kaminsky presented joint work with Patterson and Sassaman, revealing pervasive flaws in the Internet's certificate authority infrastructure.

[26] In spring of 2008, she published a paper with David Chaum and Len Sassaman[27] in a USENIX workshop[28] criticizing the lack of attention paid to user-privacy in the OLPC (One Laptop per Child) computer.

[29] Since late 2015 she has been the co-editor (jointly with the self-described Catholic social conservative anarcho-capitalist using the pseudonym ClarkHat[30]) of the Status:451 blog, which describes freedom of speech as its "founding principle",[31] and garnered attention in April 2016 for launching a successful crowdfunding campaign towards retaining the neo-reactionary blogger and entrepreneur Curtis Yarvin as speaker at the LambdaConf programming conference.

[32] She has displayed a modified version of Southern Poverty Law Center's intelligence director Heidi Beirich's assessment of Status:451 ("appears juvenile but does not seem to reflect a white supremacist organization"[32]) on her Twitter account since.

Patterson, who was diagnosed with autism in adulthood, has stated that "a single-minded focus" has helped her to have an "overwhelmingly positive relationship" with the male-dominated technology community.