Colombia’s government and the largest rebel group in the country have reached a deal to end more than 50 years of conflict, the two sides announced Wednesday, paving the way for an end to the longest-running war in the Americas.

For four years, the Colombian government and the rebels have been locked in negotiations. Time and again, they have emerged from the negotiating table to assure a weary public that another impasse had been eliminated, another hurdle cleared.

This time, the two sides declared that a final deal had been clinched.

“Today begins the end of the suffering, the pain and the tragedy of war,” President Juan Manuel Santos said in a nationally televised address after the agreement was announced. “Let’s open the door together to a new stage in our history.”

The agreement, reached in Havana where the talks took place, effectively signifies the end of the last major guerrilla struggle in Latin America.

It outlines a timetable in which the rebels, known as the Revolutionary Armed Forces of Colombia, or FARC, will abandon their arms. It also sets out a pathway in which former fighters will enter civilian life again — and in some cases, run for office.

But to most Colombians, the deal is simply a promise that the war, which has lasted 52 years, claimed some 220,000 lives and displaced more than five million people, is at last coming to an end.

Peace in Colombia now looks more likely than ever, but a big hurdle still needs to be cleared before the deal is ratified. Mr. Santos, who has staked his legacy on a deal, must now sell it to his people, who will be asked to vote in an up-or-down referendum.

Rallying against that approval is Mr. Santos’s predecessor, former President Álvaro Uribe, whose term ended in 2010 with the FARC diminished.

Mr. Uribe is widely credited with the military gains that forced the rebels to the negotiating table. But he is now leading a growing campaign against the deal, saying it amounts to an unjust amnesty for the rebels.

“They will spend zero days in prison, they will be awarded with political representation,” Paloma Valencia, a senator in Mr. Uribe’s party, said of the rebels. “This deal breaks the rule of law.”

Still, others hailed the deal as a major step for a country of 50 million people whose growing economy has long been hampered by the simple fact that the state does not control all of its territory.

“It’s an enormous opportunity for the country to create a democratic state, which will allow us to live in peace,” said Maria Emma Wills, a political analyst at the National Center for Historical Memory, a government research group.

She warned, “The deal has strong political opposition, and the next job is going to be public advocacy for it.”

The war remains one of the most emotionally charged issues in Colombia, characterized by kidnappings and the massacre of civilians caught between the rebels and the military. Waves of Colombians left the country fearing the violence. Few who remained were untouched by it.

The rebels and the government had been inching toward a final deal for months. In June, the two sides announced a cease-fire and said that the rebels had agreed to lay down their arms.

A month before, the government and the FARC declared that they had reached an agreement to release child soldiers from rebel custody, another step that helped push the negotiations toward their final stages.

Now the two sides say they have settled many of the last sticking points that kept them at loggerheads for years.

But even if the deal is approved by the public, its success is anything but guaranteed.

Will it be accepted by all rebels, who vowed to bring a Marxist revolution to Colombia but are being asked to accept far less?

How will thousands of guerrillas — many of whom were kidnapped as children and know only life in the jungle — find their way into mainstream society, and will they be accepted there?

And perhaps most crucially: Will the rebels give up not only their weapons, but their control of the lucrative drug trade as well?

The State Department calls the FARC a terrorist organization that “controls the majority of cocaine manufacturing and distribution within Colombia, and is responsible for much of the world’s cocaine supply.”

The FARC’s top commander, Rodrigo Londoño, who uses the alias Timochenko, helped set the group’s policies for “the production, manufacture and distribution of hundreds of tons of cocaine,” and for the killing of hundreds of people who interfered, the State Department adds.

Two FARC peace negotiators were named in a 2006 federal indictment, charged with helping to make the organization a narcotics powerhouse responsible for more than “60 percent of the cocaine sent to the United States.”

Still, the peace deal makes wide-ranging promises to reshape a post-conflict Colombia.

In a nod to longstanding grievances among the rebels, the government promised to make significant investments in rural areas, which the rebels say have long been neglected at the expense of cities like Bogotá.

Far more contentious, however, has been the subject of what will become of the rebels themselves.

For decades, the FARC financed its insurgency by kidnapping people and holding them for ransom, a business that terrorized thousands, including a former presidential candidate who was held for years.

The agreement tries to resolve past grievances with the stroke of a pen: Under a so-called transitional justice system, all but the most grievous crimes may be resolved with reduced sentences.

Silvio Hernández, whose son Erik was a soldier killed by the rebels in combat in 2011, said he felt the agreement would not bring justice.

“The FARC are not going to pay for the crime against my son,” he said. “It’s good that we are reaching peace, but this leaves me with many doubts.”