The Central Election Commission said Yushchenko won 51.99 percent to Prime Minister Viktor Yanukovych's 44.19 percent, according to its final preliminary vote tally — a difference of about 2.3 million votes.
Yanukovych has refused to concede defeat and says he will appeal to the Supreme Court in a bid to overturn the result. His camp says it has filed nearly 5,000 complaints about Sunday's balloting.
A similar legal challenge by Yushchenko following the fraud-tainted Nov. 21 second round runoff proved successful, leading to Sunday's unprecedented third round.
President Leonid Kuchma, in the runup to Sunday's vote, urged both candidates to accept the official result and not appeal. And the Council of Europe, the continent's top human rights watchdog, also called on Yanukovych on Tuesday to accept defeat.
"I call on all parties to accept the verdict of the ballot box and to refrain from rhetoric which may fuel division in Ukraine," said Terry Davis, the council's secretary general.
Ukraine's east-west divide has deepened during the bitter and protracted election campaign. The Russian-speaking, heavily industrialized east backed Yanukovych, while cosmopolitan Kiev and the nationalistic west supported Yushchenko.
Yushchenko has said he will aim to end the hostility between eastern and western Ukraine within two years.
"The problem is that a system has been created in which some (business) clans hold colossal power," Yushchenko said in an interview published Tuesday by Russian daily Izvestia, referring to eastern Ukraine.
"This is an Asiatic model of oligarchic rule."
Yushchenko said his first mission in office would be a trip to Moscow to try and fix "deformed" ties between the two nations.
"I must show Russia that our earlier ties were deformed, they were formed by Ukrainian (business) clans," Yushchenko was quoted as saying.
"We can and must turn this page if we are friends and are prepared to look one another in the eye."
Moscow aggressively supported Yanukovych in the first two rounds of voting in November, and is nervous about the eastward expanding EU and NATO. Russia is a giant investor in Ukrainian business, and Ukraine is a key consumer of Russian goods.
Yushchenko said both countries needed a better working relationship.
"Russia is Ukraine's neighbor. It is better to argue twice with your wife than once with your neighbor," Yushchenko told Izvestia, adding that the two nations share Slavic roots, family links, culture and language.
He said it would be difficult to bring Russia and Ukraine closer economically as long as there were significant "disconnects" in their tax and trade policies.
As for the common market Moscow wants with Ukraine, Belarus and Kazakhstan, Yushchenko urged caution, alleging that details of the plan were shrouded in secrecy.
The opposition leader, a former Central Bank chief, has pledged to bring this nation of 48 million people closer to the West by earning it a bigger role in international bodies such as the European Union. He says that under his leadership, Ukraine could aim for associate membership with the European Union in three to five years.
But in a move unlikely to win Yushchenko support in the east, his most radical ally, Yulia Tymoshenko, planned to head to Donetsk on Tuesday. Tymoshenko is widely unpopular in the region and she has pledged to crack down on powerful tycoons there who are becoming increasingly assertive in politics.
She has said she would like the prime minister's job in a Yushchenko administration.
In Kiev, Yushchenko supporters vowed to remain at their "Free Kiev" tent camp on the capital's main avenue until Yushchenko's inauguration.
"Ukraine is no longer the same. The whole world has seen us gaining freedom and democracy," said protester Mykola Yushchenko, wearing an orange handkerchief around his head.