The Biden administration, escalating its fight with Republican governors who are blocking local school districts from requiring masks to protect against the coronavirus, will use the Department of Education’s civil rights enforcement authority to deter states from banning universal masking in classrooms, Secretary of Education Miguel Cardona said Wednesday.

The move puts the department at the center of bitter local debates over how to mitigate against the coronavirus in schools, just as the highly infectious Delta variant is fueling a spike in pediatric cases. Mr. Cardona said he was acting at the direction of President Biden, who is scheduled to speak about the pandemic later Wednesday and to instruct the department to use all of its powers to ensure a safe return to in-person learning this fall.

“The president is appalled, as I am, that there are adults who are blind to their blindness, that there are people who are putting policies in place that are putting students and staff at risk,” Dr. Cardona said in an interview on Wednesday, referring to bans on mandatory masks in schools in more than half a dozen states.

“At the end of the day,” he said, “we shouldn’t be having this conversation. What we’re dealing with now is negligence.”

The Centers for Disease Control and Prevention recommends that everyone in schools wears masks, regardless of vaccination status, so that schools can more safely resume in-person instruction. A vast majority of counties across the United States are experiencing either “substantial” or “high” transmission rates that call for indoor mask-wearing even among the vaccinated, according to the C.D.C.

Invoking the Education Department’s civil rights enforcement arm marks a major turning point in the Biden administration’s effort to get as many students back to in-person schooling this fall, and the urgency felt nationwide about blunting the impact of a pandemic has wreaked havoc on students’ educational careers since March 2020.

The nation’s most vulnerable students, namely students with disabilities, low-income students and students of color have suffered the deepest setbacks when districts pivoted to remote learning, and their disproportionate disengagement have long drawn concern from education leaders and civil rights watchdogs.

Under Section 504 of the Rehabilitation Act of 1973, students are entitled to a Free Appropriate Public Education, known as FAPE, and Title VI of the Civil Rights Act of 1964 prohibits discrimination based on race, color and national origin.

The department could initiate its own investigations into districts, if state policies and actions rise to potential violation of students’ civil rights. It could also review complaints from parents and advocates who make the case that denying students the ability to wear masks is, in effect, a civil rights violation because it could deny a student their right to an education by putting them in harm’s way in school. Such investigations could result in resolution agreements, as many investigations by the office often do, and in the most extreme cases result in revocation of federal funding.

Dr. Cardona said conversations with parents of children with autism, respiratory illness or weak immune systems, “who rely on school for socialization and the important building blocks of learning,” had contributed to his sense of urgency.

“I’ve heard those parents, saying ‘Miguel, because of these policies, my child cannot access their school, I would be putting them in harm’s way,” Dr. Cardona said. “And to me, that goes against a free appropriate public education. That goes against of the fundamental beliefs of educators across the country to protect their students and provide a well rounded education.”

The administration will also send letters to six states — Arizona, Iowa, Oklahoma, South Carolina, Tennessee and Utah — admonishing governors’ efforts to ban for barring universal masking in schools.

Last week, Dr. Cardona sent similar letters to the governors of Texas and Florida, reminding them that districts had both the funding and the discretion to implement safety measures that the C.D.C. recommended for schools. The secretary also made clear that he supported district leaders who defied the governors’ orders.

In his letter to Texas, Mr. Cardona warned that the state was jeopardizing its federal relief funding. The state’s attorney general, Ken Paxton, doubled down in response, suggesting on Twitter that he would take the state’s ban on school mask mandates to the Supreme Court.

Dr. Cardona, who has been traveling around the country to promote the administration’s school reopening agenda , signaled he had lost his patience with students and desperate parents being at the mercy of partisan politics, even in places where the virus is surging.