Benioff added that though the Valley is the home of "an incredible technology industry" that "every city in the world craves," some executives in the sector are ignoring issues such as gentrification and homelessness.
"In some ways, San Francisco is the canary in the coal mine," Benioff said in an interview with CNBC's Sara Eisen at the World Economic Forum in Davos, Switzerland. "We have to look at San Francisco and say here's the best technology example in the world and yet the worst homelessness."
"San Francisco is kind of a train wreck, we have a real inequality problem," he said. "It's because of the tech sector."
A one-night count of San Francisco's homeless population in 2017 showed that roughly 7,500 people were without homes, according to figures released by the city in June.
In California as a whole, separate figures from the U.S. Department of Housing and Urban Development showed there were 134,000 homeless people statewide on any given night in 2017. The number of homeless Californians jumped 13.7 percent in 2017 from the previous year.
The Salesforce chief was a vocal proponent of Proposition C, a bill aimed at fighting homelessness by raising taxes on big businesses in San Francisco. The measure was passed in November and is expected to generate up to $300 million in new tax revenue to tackle the city's homelessness crisis.
Benioff entered a battle of words over the proposal on Twitter with the social network's CEO Jack Dorsey last year after the latter made his view known that Prop C was not the "best way" to address homelessness in San Francisco and California as a whole.
"Prop C was a great example of where we had people who were very committed to getting that done and improving things in San Francisco," Benioff said Tuesday. "Each CEO is responsible for their little part."
He said that "not every CEO" was committed to fighting inequality, and some were in fact battling "tooth and nail" to defeat Prop C. Benioff added that his criticism was not limited to Dorsey.
Other tech entrepreneurs, including Stripe CEO Patrick Collison and Zynga founder Mark Pincus, also opposed Prop C. Critics backing the campaign No on Prop C claimed it lacked accountability and oversight.
For his part, Dorsey said the proposition would unfairly treat his financial services firm Square and Collison's Stripe, claiming they would have to pay disproportionately more in tax than the likes of Salesforce.
Microsoft recently raised the alarm on the issue of homelessness, but not in California. The Redmond, Washington-based software giant earlier this month committed $500 million to build more affordable housing in Seattle.