After two days of tributes in Havana, hundreds of thousands of flag-waving Cubans lined the streets to bid farewell as a military jeep began a four-day journey on Wednesday morning with the cedar urn in tow.
Crowds chanted "I am Fidel!" as the convoy started retracing the victory tour that Castro's guerrilla took in 1959 to celebrate their defeat of US-backed dictator Fulgencio Batista.
The flag-covered urn, which rested under a glass case on a small olive-green trailer, arrived in Santa Clara after midnight and entered a complex with a mausoleum and museum dedicated to Guevara.
A somber guitar, song and dance show played across a giant statue of Guevara as the "caravan of freedom" paused a third of the way into its 950-kilometer (590-mile) trek across the island.
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The convoy will resume today, heading to other cities before a final ceremony on Sunday in the eastern city of Santiago de Cuba, where Castro's ashes will be laid to rest next to 19th century independence hero Jose Marti.
Cubans were observing the fifth of nine days of mourning for Castro following his death on Friday at age 90. Castro ruled from 1959 until an illness forced him to hand power to his brother Raul in 2006.
"I come from a poor family. I am black. In another era, I wouldn't have had the opportunity to be who I am today," said Maria Gonzalez, a 31-year-old computer engineer.
Castro met Guevara in 1955 while in exile in Mexico, and the young doctor joined Fidel and Raul on the boat that took them to Cuba a year later.
Guevara won a crucial battle in Santa Clara in 1958, derailing an armored train and taking the city.
His remains were recovered three decades later and taken to Santa Clara, now home to a huge statute of Che and a museum dedicated to the revolutionary icon.