Chadema presidential candidate says figures being announced by the National Electoral Commission (NEC) cannot be verified.
Lissu said his party will not accept the vote outcome and called on the masses to "take the matter in their own hands" by engaging in peaceful demonstrations.
Zitto Kabwe, the party leader of ACT-Wazalendo, said the elections had confirmed Tanzania's growth into a dictatorship.
Tanzania's main opposition candidate Tundu Lissu on Thursday rejected the results of the vote, terming it as a fraud.
At a press conference in Dar es Salaam, Lissu, who ran on the Chama Cha Demokrasia na Maendeleo (Chadema) ticket, said the figures being announced by the National Electoral Commission (NEC) cannot be verified.
“There was unprecedented levels of fraud and use of force in this election that stole the will of the people to elect the leaders of their choice. What we witnessed on Wednesday defeats even Tanzania’s own laws and regulations that govern elections,” said Mr Lissu from his Tegeta home in Dar es Salaam.
"We do not recognise what happened yesterday (Wednesday)…because it was marred by irregularities in all stages.
"The results that have been announced since yesterday and which the Electoral Commission continues to announce today are therefore illegitimate. They do not reflect the true will of the millions of Tanzanian people who turned up at their polling stations."
Mr Lissu said his party will not accept the vote outcome and called on the masses to "take the matter in their own hands" by engaging in peaceful demonstrations.
Preliminary results from polling stations show the incumbent Joseph Magufuli leading. In some stations, Dr Magufuli has nearly five times the vote compared to the total garnered by all the other 14 presidential contenders.
But Chadema and several other opposition politicians said the vote had been rigged in favour of the ruling Chama Cha Mapinduzi.
Zitto Kabwe, the party leader of ACT-Wazalendo, said the elections had confirmed Tanzania's growth into a dictatorship.
"Tanzania in full-blown one-party dictatorship. We shall resist this," he said on Thursday.
"I urge Tanzanians not to recognise any authority coming out of these widespread rigging. I ask the international community not to recognise this Tanzanian election. Consequences for this must be huge."
The NEC chairperson, retired appellate court judge Semistocles Kaijage has rejected the accusations of fraud. But Mr Lissu said the "election should not be given any form of legitimacy by the international community."
"We ask friends of Tanzania not to confer any recognition to these illegitimate results," he added.
NEC and the Zanzibar Electoral Commission have started announcing presidential, parliamentary and civic results, which show that the ruling party is headed for a landslide win in all the electoral areas.
Final outcome
In Tanzania, presidential election results announced by the electoral commission cannot be challenged in court. It means the figures, once confirmed by the Commission remain final.
This is despite an order from the African Court of Human and People's Rights last July ordering the Tanzanian government to amend the Constitution and allow every election results to be contestable in a court of law. The decision had been made, however, a year after Tanzania withdrew from clauses of the Court which had allowed individuals to sue their government at the African institution.