De Leon received the California Democratic Party's nomination for the Senate seat in July, but Feinstein leads in public polling as she seeks her sixth term.
It was Feinstein's first appearance with an election opponent since 2000.
The two Democrats faced off at the non-partisan Public Policy Institute of California in San Francisco. The group's president, Mark Baldassare, moderated the debate.
They sparred over a range of issues, from immigration to housing to who is best suited to fight against President Donald Trump.
"I think growing the economy is important - doing those things that educate our people to take better jobs, to produce better incomes, being able to build homes for people that they can afford is important," Feinstein said.
De Leon said he is the person best equipped to fight back against Trump's Republican policies, particularly on his strong anti-immigration stance.
"We are engaged in the battle for America's soul against a president without one," de Leon said. "I believe that the status quo in Washington is either unwilling or incapable of fighting back.:
Feinstein has about $4 million left in her campaign to spend compared to de Leon's less than half a million.
The Associated Press contributed to this report.