[7] In June 2012, GiveWell announced a close partnership with Good Ventures, the philanthropic foundation tasked with giving away Facebook co-founder Dustin Moskovitz's wealth.

Karnofsky's claim that the incident had been due to sleep deprivation and offer to donate to MetaFilter were mocked by users of the site.

[19] Karnofsky was CEO and then co-chief executive officer of Open Philanthropy, a research and grantmaking foundation whose main funders are Cari Tuna and Dustin Moskovitz.

[21][22][23] As of August 2019, Open Philanthropy has made around 650 grants to over 370 unique organizations, disbursing a total of $857 million.

In recent years, he has written about the importance of extending empathy to all beings deserving of moral consideration, even when it is unusual or seems strange to do so.

[36] In August 2014, after the William and Flora Hewlett Foundation announced the end of its Nonprofit Marketplace Initiative (one of GiveWell's major early funders), Karnofsky wrote a post on the GiveWell blog offering his thoughts on the program, informed by his experience as a recipient of its largesse.

[38] Karnofsky has shared his thoughts on altruistic career choice and elaborated on Open Philanthropy's approach to cause prioritization in an interview with Robert Wiblin for the 80,000 Hours podcast[39] as well as elsewhere.