SANTA CRUZ, Bolivia— Pope Francis issued a broadside against the global economic system, denouncing a structure based on worship of money, blaming it for inequality, military conflict and environmental degradation.

Speaking Thursday in a bastion of the antiglobalization movement, the pontiff called for a “globalization of hope” that would guarantee the needs of every person. He urged those who are excluded themselves to rise up to realize that hope.

Pope Francis illustrated the world’s problems in personal terms, invoking the “endangered peasant, the poor laborer, the downtrodden native, the homeless family, the persecuted migrant, the unemployed young person, the exploited child…”

Such cases are not isolated issues but casualties of a system that has “imposed the mentality of profit at any price, with no concern for social exclusion or the destruction of nature,” he told a group of several thousand grass-roots social activists from Latin America and around the world, while sitting alongside Bolivian President Evo Morales.

Moments before, Mr. Morales recounted his country’s struggle with the International Monetary Fund and the “democratic revolution” that Greek voters had recently initiated by rejecting the terms of their European creditors.

“In Bolivia, the gringos no longer rule, the Indians do,” Mr. Morales said, wearing a jacket with the image of the Argentine revolutionary Che Guevara.

The pontiff’s criticism—an indirect reproach of the West and the U.S., which he will tour later this year—was the most directly political so far on his weeklong visit to South America, which started on Sunday in Ecuador and will also take him to Paraguay beginning on Friday.

It was the second such meeting co-sponsored by the Vatican in which Pope Francis addressed his signature concerns for social and economic justice.

Thousands of people lined the nearly mile-long stretch of road leading up to the meeting place, including Morales supporters.

“The pope is a Jesuit so he knows the struggle of the indigenous,” said Juan Antonio Cabrera, who came from the pope’s native Argentina. “He’s lived and worked with them. He’s spreading the same message as Jesus did.”

Others were critical of Mr. Morales, who has ruled Bolivia for a decade.

“The government must be nervous that the pope may find out what’s really going on here,” said an indigenous leader, Adolfo Chávez, who raised concerns about a deadly state crackdown in 2011 on groups protesting a new highway cutting through pristine indigenous park land.

In his speech, Pope Francis blamed many of the global system’s ills on “corporations, loan agencies, certain ‘free trade’ treaties, and the imposition of measures of ‘austerity’ which always tighten the belt of workers and the poor.”

In a country that has broken most ties with U.S. anti-drug efforts, the pope denounced what he characterized as burdensome and counterproductive measures imposed on poorer countries “under the noble guise of battling corruption, the narcotics trade and terrorism.”

The pope urged his audience to “say ‘no’ to an economy of exclusion and inequality” in favor of an “economy of Christian inspiration,” which would guarantee everyone not only the basics of land, housing and employment, but also “access to education, health care, new technologies, artistic and cultural manifestations, communications, sports and recreation.”

Pope Francis termed his goal the “globalization of hope, a hope which springs up from peoples and takes root among the poor, and must replace the globalization of exclusion and indifference.”

That goal, the pope said, “is no utopia or Chimera. It is an extremely realistic prospect. We can achieve it.” He urged his audience of farmers, artisans, rag-pickers and un-unionized workers to join “in the great processes of change” through political participation and forms of “communitarian production” such as workers’ cooperatives.

“I am with you,” the pope told the crowd.

Pope Francis acknowledged that the Catholic Church he leads has a mixed record as force for social liberation, particularly in Latin America, whose conquest by European colonists was justified in the name of spreading Christianity.

“I humbly ask forgiveness, not only for the offenses of the church herself, but also for crimes committed against the native peoples during the so-called conquest of America,” the pope said, though he noted the good works of many missionaries that he said made the church “part of the identity of the peoples of Latin America.”

On Wednesday evening in Bolivia’s capital of La Paz, Mr. Morales made an especially provocative gesture when he gave the pope a wooden crucifix that incorporated the communist symbol of the hammer and sickle, and draped him with two medallions, one of which also bore the former Soviet image.

A Vatican spokesman said the crucifix was designed by the late Rev. Luis Espinal, an activist Jesuit priest killed by paramilitary forces in 1980, when Bolivia was under a dictatorship.

The hammer-and-sickle medallion is an honorary decoration established by the Bolivian government in honor of Father Espinal, the spokesman said.

Pope Francis paused briefly to pray at Father Espinal’s murder site on Wednesday evening.

“I am here to greet you and to remember a brother of ours who was a victim of interests that didn’t want Bolivia’s freedom,” the pope said at the site. “He bothered them, and they eliminated him.”

Asked about reports that Pope Francis had rebuked Mr. Morales for the gift, the spokesman told reporters he didn’t think the pope had “made a particular judgment” about the object. He noted that Pope Francis has spoken frequently against the ideological exploitation of religion, but just as frequently for openness to dialogue with different systems of thought and belief.

As a Jesuit priest and bishop in Argentina in the 1970s and ‘80s, Pope Francis embraced versions of so-called liberation theology that affirmed the church’s “preferential option for the poor,” but distanced himself from elements in the movement that adopted Marxist concepts such as “class struggle,” which also drew censure from the Vatican’s doctrinal office.