Newsom interviewed Charlie Kirk for more than an hour and 20 minutes on his podcast, "This is Gavin Newsom."
During the conversation, Kirk brought up the Democratic Party's support for transgender athletes competing in women's sports.
"So like you right now should come out and be like, 'You know what, the young man who's about to win the state championship in the long jump in female sports, that shouldn't happen.' You as the governor should step out and say no," Kirk said.
Newsom responded by saying those situations are "deeply unfair."
"Well, it's I think it's an issue of fairness," Newsom said. "I completely agree with you on that... It's easy to call out the unfairness of that. There's also a humility and a grace. You know that these poor people are more likely to commit suicide, have anxiety and depression and the way that people talk down to vulnerable communities is an issue that I have a hard time with as well. So both things I can hold in my hand. How can we address this issue with the kind of decency that I think you know it's inherent in you?"
Newsom's statement quickly spurred the nation's largest LGBTQ+ civil rights group, the Human Rights Campaign, to send a warning shot across Newsom's bow in regard to a possible run for the presidency.
The group released a statement that reads in part, "The path to 2028 isn't paved with the betrayal of vulnerable communities... it's built on the courage to stand up for what's right and do the hard work to actually help the American people."
The governor's statement marked a bit of a U-turn for Newsom, who, as Mayor of San Francisco 20 years ago, defied state law and allowed same-sex couples to marry.
Current California law allows transgender athletes to play on school teams that are consistent with their gender identity.
Crowds surrounded Kirk as he spoke on the Cal State Northridge campus as part of his "American Comeback" tour.
Supporters of his and protesters against him packed the quad near the University Student Union.
Some student demonstrators were unhappy with Newsom's transgender shift.
"I think at the end of the day, Newsom is a politician, and I think that politicians are going to do what's best for them. I think that him siding with Charlie Kirk is the best for him in his mind," CSUN sophomore Madeline Burton said.