"There is a war on faith in America today," Cruz said, later noting that 54 million evangelical Christians stayed home during the 2012 election.
"I'm here to tell you, we will stay home no longer," he said as the audience, which filled a ballroom and the campaign estimated to number 2,500 people, cheered.
Earlier in the day, Cruz and actress Ellen Page sparred over gay rights at the Iowa state fair.
Cruz, who is attempting to paint his candidacy as an insurgent insider -- a senator who relishes fighting both Republicans and Democrats and in recent weeks accused Senate Majority Leader Mitch McConnell of lying -- echoed a theme of the event: if forced to choose between fidelity to God and the government, people here will choose God.
"If we cannot worship God, if we cannot live according to our faith .... all other liberties fade away," Cruz said.
The event highlighted the stories of people "victimized by government persecution," according to Cruz's Web site, including a former Air Force sergeant who said he was fired because of his religious views on gays, a former Atlanta fire chief who said he was fired for his religious beliefs and an Iowa couple who refused to host a same-sex wedding. Cruz lauded them as "heroes."
The Texas Republican and others here, including members of his Iowa leadership team, told the audience that it may not be a matter of if, but when, they have their religious liberties threatened.
"Is the next victim of persecution your pastor?" Cruz asked. "Your charity, where you volunteer your time at a crisis pregnancy center?"
Cruz interviewed the couple, Dick and Betty Odgaard, in a video and on stage at the Iowa Events Center. Cruz cited scripture and held Betty Odgaard's hand as she cried recounting the backlash over refusing to host a same-sex wedding. The couple was sued and closed their business earlier this year.
The Texas Republican also had a conversation on stage with Naghmeh Abedini, the wife of Saeed Abedini, a pastor from Idaho who has been in Iranian custody since 2012. He was later convicted of security-related charges that include claims of proselytizing.
Cruz has said that 2016 will be a "religious liberty election," and is working to woo the religious right, which has a strong constituency here, in the early voting state of South Carolina and in the rest of the South, which is set to play a major role in the Republican nominating contest.
Here in Iowa, 57 percent of Republican caucus-goers identified as evangelical Christians, according to entrance polls. Cruz has been courting faith leaders here, dispatching his father Rafael, a pastor, to speak at events around the state and announcing Friday that he wants to recruit a pastor in each of Iowa's 99 counties to do faith outreach.
Cruz's Iowa campaign chairman, Matt Schultz, suggested Cruz was chosen by God.
"We're at a crossroads in our country," Schultz said, stating that God prepares men and women to stand up and fight at certain times. "Ted Cruz is the man who God has prepared for this moment in time to be our champion, to fight for our husbands, our wives, our children, and our grandchildren, for our country."
While Cruz will be competing for the evangelical vote with candidates including former Arkansas governor Mike Huckabee, former senator Rick Santorum and neurosurgeon Ben Carson, few have been as vociferous about the notion that religious liberty is under attack than Cruz. He brought up the issue repeatedly during a bus tour of the South last week, repeatedly promising that on his first day in office he would direct federal agencies not to meddle with people who believe they have stayed firm to their religious beliefs in the face of social change.
“The persecution of religious liberty ends today,” Cruz said to cheering crowds from the altar of a church in Chattanooga, Tenn., an outdoor stage in Little Rock and the flatbed of a pickup truck in Tupelo, Miss.
Here in Des Moines, the rally featured a performance by the Christian rock band the Newsboys. Attendees could pick up free American flags, coloring books titled "We "C" Ted Cruz for President" and a Ted Cruz pocket Constitution. A ministry handed out black rubber bracelets.
The issue of religious liberty has come to the fore of the presidential campaign after Indiana and Arkansas passed religious liberty laws and the Supreme Court ruled that gay couples have the right to marry nationwide. Cruz has used the issue of religious liberty to highlight the persecution of Christians, defend traditional marriage and the right to life.
Cruz, a former Supreme Court clerk, excoriated the court in the wake of the gay marriage ruling and continued to do so Friday. The former solicitor general of Texas and a lawyer in private practice, he talked about two cases he won by a 5-4 margin at the court, one that involved the Ten Commandments at the Texas state capitol and a cross at a Mojave Desert veterans memorial.
“You want to know what this election is about?" Cruz asked. "We’re one justice away from the Supreme Court saying every image of God shall be torn down.”