The 83-year-old pope appeared alert, but clearly weakened during the 2½-hour service honoring two clerics imprisoned and tortured under Slovakia's former communist regime.
He slurred his words and turned over his homily to a cardinal to complete. Bidding farewell at the airport before departing for Rome, the pope struggled to catch his breath.
His Parkinson's disease, and the hip and knee ailments that keep him from even standing, clearly are taking a toll and forcing major changes in John Paul's routine as he approaches the 25th anniversary of his pontificate.
Still, his mere presence drew cheers from the large crowd filling a plaza near a sprawling communist-era housing project.
"I greet you, beloved Slovak people," he said as people waved Slovak and yellow-and-white Vatican flags.
Vatican spokesman Joaquin Navarro-Valls told reporters that while the pope's health problems were obvious, "it is very moving how he has incorporated the physical limitations into the way he performs his ministry."
Navarro-Valls insisted they "don't hamper in any way the way he performs his duties."
Slovak Bishop Rudolf Balaz said, "The fact that the pope can't read his whole sermon is a chronic matter — but he communicates with us."
The Vatican has been adapting to the pope's deteriorating condition. He now uses lifts to get on and off planes and sits in a throne-like chair on wheels that allows him to celebrate Mass while seated.
One of the last times John Paul was seen standing in public was in June, when he rose from his chair with great difficulty to greet visiting Secretary of State Colin Powell.
His difficulty communicating raised a new problem.
Upon landing Thursday in Slovakia, John Paul was unable to complete his arrival remarks for the first time in 102 foreign trips, forcing the Vatican to scramble to find someone to read them.
"People come with great expectations, and he can read only three sentences. That's disappointing," said pilgrim Sidonia Sedlackova, 55. "Spiritually, he is still well, but his body can't cope. I would not recommend that he take other trips like this."
The Slovakia visit was John Paul's last scheduled trip, although he has invitations for next year from at least four countries including France, Austria, Switzerland and the pope's native Poland.
Asked whether Slovakia would be John Paul's last trip, Navarro-Valls replied: "I don't think so. Knowing the Holy Father, it is very difficult to say it will be the last trip of his pontificate."
Although such top Vatican officials as Secretary of State Cardinal Angelo Sodano have raised questions about travel, the decision rests with John Paul. He has pressed ahead despite his ailments, as well as brushing aside any suggestion he step down.
Navarro-Valls said the pope has often joked that when he wants to find out about his health he reads the newspapers.
Sunday's final service had an appropriate backdrop: the sprawling Bratislava housing complex of Petrzalka, a bleak jumble of high-rises built during communism and nicknamed the Slovak Bronx.
"It was built without churches by the totalitarian regime, which wanted it to be a city without God," Archbishop Jan Sokol said.
A new Catholic church is being built in the neighborhood.
The country's church suffered intense persecution under communism, which ended in 1989. Many priests were ordained in secret, and hundreds were imprisoned or sentenced to forced labor by the regime, which confiscated church property.
Among them were Greek Catholic Bishop Vasil Hopko and Roman Catholic Sister Zdenka Schelingova. The Vatican intended their beatification Sunday to serve both as a solemn reminder of oppression and a triumphant celebration of the church's ability to endure and even thrive.
Beatification is the last step before possible sainthood.
Today, nearly seven in 10 of Slovakia's 5.4 million people are Roman Catholics.
"I thank God because you have been able to safeguard, even in difficult times, your fidelity to Christ and to his church," John Paul said.