More than three-quarters of the 37 million voters cast their ballots on Sunday, with around 52% supporting Yushchenko while just over 44% backed Prime Minister Viktor Yanukovich.
But Yanukovich charged that the vote was riddled with irregularities and his campaign vowed to appeal against the results to the Supreme Court - just like Yushchenko did in November.
"I will never acknowledge such a defeat because the constitution and human rights were violated," he said in televised remarks. "We have lost nothing."
However observers said that, unlike Yushchenko's appeal, Yanukovich will not be able to derail the election with legal challenges because of the opposition leader's formidable lead in the ballot count.
The legal claims could delay for weeks an official declaration of Yushchenko as the winner of Sunday's vote, as the law prohibits such an announcement until all legal appeals have been exhausted.
More than 12,000 observers had been registered to monitor Sunday's election.
The Organisation for Security and Cooperation in Europe (OSCE), which had slammed the November election for irregularities, said that Sunday's vote brought the country substantially closer to meeting international democratic election standards.
"Yushchenko was declared president even before the elections"
But Bruce George, head of the OSCE international election observer mission in Ukraine, told a news conference: "That is not to say the election was perfect. It was not."
In his first comments after the close of polls, a beaming Yushchenko addressed dozens of journalists crammed into his campaign headquarters early on Monday as official returns showed him carrying an unassailable lead.
"It has happened," he said to wild cheers. "For 14 years we have been independent, but now we are free. This is a victory for the Ukrainian people, for the Ukrainian nation," said the 50-year-old former prime minister and banker.
Reaction from around the world to Yushchenko's apparent election triumph was varied.
EU foreign policy chief Javier Solana congratulated the people of Ukraine and paid tribute as well to the country's political leaders who he said had "acted with a high degree of responsibility to set their country firmly in the path of democracy".
But Moscow's media took a defeatist look on Monday at Yushchenko's victory in Ukraine's crunch election.
"Yushchenko was declared president even before the elections," the Nezavisimaya Gazeta, a centrist newspaper, wrote in reference to Sunday's vote.