WASHINGTON — House and Senate negotiators reached a landmark agreement on Tuesday that would strip military commanders of most of their authority to prosecute sexual assaults and myriad other criminal cases, a move that Pentagon leaders, lawmakers and presidents have resisted for nearly a generation.

The legislation, part of a broad defense policy bill, comes after nearly two decades of efforts by female lawmakers and survivors’ groups, and in spite of fierce last-minute lobbying against the proposal by military lawyers.

Under the agreement, independent military prosecutors would replace commanders in determining whether those accused of sexual assault, rape, murder, domestic violence and an array of other offenses would be prosecuted. Sexual harassment would be criminalized, but would not fall under the special prosecutor structure, a concession to opponents of the changes.

The measure does not go as far as Senator Kirsten Gillibrand, Democrat of New York, has long sought, and she vowed to fight for further changes in the new year.

But the new system would be a sea change in the approach to the intransigent issue of sexual assault in the military.

Don Christensen, a former chief prosecutor of the U.S. Air Force who is now president of Protect Our Defenders, a nonprofit organization that has worked on the issue for a decade, called the new legislation “the most significant military justice reform in our nation’s history.”

Under current law, commanders have the authority to determine which cases are referred to courts-martial, the pool of eligible jurors and the scope of clemency requests.

Under the new agreement, “special trial counsel” would be tasked with assessing the cases covered by the legislation and have the exclusive authority to refer them to courts-martial.

Each military service would have a lead special trial counsel who would report directly to the secretaries of the Army, Navy and Air Force, rather than judge advocate generals within the military, an issue that became a last-minute sticking point. Those pushing for changes to the current system argued that civilian leaders appointed by the president and answerable to Congress must hold that role.

Commanders will maintain their authority to conduct the trials, choose jury members, grant immunity, and approve witnesses, conditions that proponents say were technically necessary to ensure due process and the fair administration of military justice.

But Ms. Gillibrand said that component rendered the new legislation insufficient. “Removing that authority from commanders is critical,” she said in a statement.

“This bill represents a major setback on behalf of service members, women and survivors in particular,” she said. “However, we will not stop seeking true military justice reforms for our brave service members and I will continue to call for an up or down floor vote.”

The compromise legislation would also require the Pentagon to track instances of retaliation across the Department of Defense and enact significant changes to how sentencing is handled.

The efforts reflect generational changes in the armed services, with younger members speaking out more forcefully against the current system, and shifting views among lawmakers in both parties who have complained about the Pentagon’s tepid response — and lack of progress — to assault.

Defense Secretary Lloyd J. Austin III had been deeply disturbed by the shortcomings of the current system during his years as an Army general. Both he and President Biden this year came out in support of changing how the military handles sexual assault cases.

“While not perfect, the agreement is far from a setback for survivors and their advocates,” said Lynn Rosenthal, the chairwoman of an independent review commission that Mr. Austin appointed this year to come up with recommendations on the issue. “Instead, it represents a historic step toward justice.”

General Mark A. Milley, the chairman of the Joint Chiefs of Staff, had long opposed the changes but acknowledged last spring that junior enlisted troops had largely lost faith that sexual assault cases would be handled fairly.

The movement gained momentum last year after the death of Vanessa Guillen, an Army specialist who law enforcement officials said was killed by another soldier at Fort Hood in Texas. The case set off a deep examination of the culture of the Army base and the broader military in which assault has remained pervasive. Years of small legislative steps have done little to stem the problem, and Ms. Gillibrand, as well as Representative Jackie Speier, Democrat of California, who had also worked on legislation for years, were often rebuffed by fellow lawmakers and Pentagon officials.

Senator Joni Ernst, Republican of Iowa and a retired National Guard lieutenant colonel, said her own experience with sexual assault informed her views on the issue, which in turn influenced other Republicans to support such efforts this year.

The new law will take two years to roll out, lawmakers said.

In 2019, the Defense Department found that there were 7,825 reports of sexual assault involving service members as victims, a 3 percent increase from 2018. The conviction rate for cases was unchanged from 2018 to 2019; 7 percent of cases that the command took action on resulted in conviction, the lowest rate since the department began reporting in 2010. An independent 2020 review found that more than 30 percent of charges of penetrative sexual offense should not have been brought to trial because of insufficient evidence.

“Though this agreement clearly does not include everything my colleagues and I pushed for,” Ms. Speier said, “it is a giant leap forward for survivors of sexual assault and marks a watershed moment in the fight for justice for those failed by the current system, and the family members of those slain or who died by suicide as a result of that failure.”