"I’d put my record up against anyone’s," the long-serving senator replied.
Blum, a philanthropist, was married to the California Democrat for more than four decades.
But Newsom enjoys several advantages in the deep blue state, including a huge war chest and a lack of well-known challengers.
It's a major change for the California Democrat, who has long been opposed to changing the Senate procedure.
Gov. Gavin Newsom had said if the senator were to step down early, he’d nominate a Black woman to her seat.
There are now no Black women in the U.S. Senate since Kamala Harris became vice president.
The California secretary of state has emerged as the front-runner to replace Vice President-elect Harris in the Senate.
California Gov. Gavin Newsom (D) is under pressure to appoint either a Black woman, a Latino or a member of the LGBTQ community.
The California Democrat's announcement comes after progressives expressed anger at her handling of Supreme Court Justice Amy Coney Barrett's hearings.
The California senator angered liberal groups after she praised Trump's Supreme Court nominee and the GOP senator in charge of confirmation hearings.