"This government is already eight years old. It's an old, bad, lying government, and it must go on December 3," Manuel Rosales told the demonstrators on Saturday.
Rosales, governor of oil-rich Zulia state, described the march as an "opposition avalanche" as an estimated 10,000 of his supporters gathered in downtown Caracas.
Rosales accused Chavez's government of mismanaging the country's oil wealth and ignoring crime.
He also said that Chavez's close friendship with Fidel Castro, the Cuban leader, was leading Venezuela towards a similar international isolation.
"They say the Venezuelan people rule - that's a lie," said Rosales.
"[We have] a government that is a puppet of a communist, totalitarian system. ... We have a government that is governing from Cuba."
Caracas' metropolitan police estimated the crowd at about 9,000, but reporters on the scene estimated the turnout was over 10,000.
Rosales also slammed the government's record on crime, claiming that murders, kidnappings and other crimes in the South American country have sharply risen since Chavez took office in 1999 - an issue that recent polls show is a top concern among Venezuelans.
He also accused Chavez of giving away millions of dollars in aid and donations to countries around the world, while many Venezuelans remain impoverished.
"There is a paradox in this country: poor people and a very rich government. The people don't want any more crumbs," Rosales said.
He promised that, if elected, his government that would distribute Venezuela's oil wealth at home and try to attract more foreign and internal investment.
Rosales also appeared to rule out a boycott of the December 3 presidential election, urging people to vote despite worries about vote-rigging and new electronic voting machines.