The opposition demonstrations come after two weeks of violent protests that have left five people dead and dozens wounded.
Thousands of Maduro opponents streamed to 26 rally points around Caracas ahead of what their leaders vow will be the "mother of all protests" calling for the leftist president's ouster.
"We have to end this dictatorship. We're fed up. We want elections to get Maduro out, because he's destroyed this country," said protester Ingrid Chacon, a 54-year-old secretary.
Wearing white and brandishing the red, blue and yellow of Venezuela's flag, the protesters planned to march on the city center -- a pro-government bastion where red-clad Maduro supporters were massing for a counter-demonstration.
The rival demos come after two weeks of violent protests that have left five people dead and dozens wounded, according to officials.
Sowing fears of more violence, Maduro has urged his supporters, the military, and civilian militias to defend the socialist "revolution" launched by his predecessor Hugo Chavez in 1999.
It was unclear whether rival demonstrators would come face to face. Soldiers blocked key roads into the capital, and some 20 subway stations were closed.
Opposition leaders accused the authorities of trying to intimidate them with the heavy security presence.
They accuse the security forces of repression and the government of sending groups of armed thugs to beat up protesters.
It is set to be the biggest day of protests since Venezuela's crisis escalated on March 30, when the Supreme Court tried to take over the powers of the National Assembly.
The assembly has been the only lever of power Maduro's camp does not control since the opposition won a landslide in legislative elections in 2015.
The streets of Caracas have seen running battles pitting masked protesters hurling stones and Molotov cocktails against riot police firing tear gas, rubber bullets and water cannon.
The protests have been relatively small so far, with turnout in the thousands.
But the opposition is now hoping to flood the streets with protesters, whom they are urging to remain peaceful.
Maduro's camp vowed not to be outdone.
"The whole of Caracas will be held by the revolutionary forces," said lawmaker Diosdado Cabello, one of the president's most powerful allies.
Pressure on Maduro has increased as falling prices for Venezuela's crucial oil exports has aggravated an economic crisis, creating severe shortages of food and medicine in the state-led economy.
On Tuesday, the center-right opposition repeated its call for the military -- a pillar of Maduro's power -- to abandon him.
"It is the moment for the armed forces to demonstrate that they are with the constitution and with the people," said Julio Borges, the speaker of the legislature.
But the defense minister, General Vladimir Padrino Lopez, pledged the army's "unconditional loyalty," while Maduro blasted Borges for inciting a "coup."
The president rallied his troops this week, sending the army into the streets and ordering pro-government militias to be expanded to half a million members, "each with a rifle."
"The hour of combat has arrived," Maduro said.
In Latin America, where other governments are increasingly alarmed by Venezuela's instability, 11 countries including Brazil, Mexico and Chile issued a statement Monday condemning the deaths of protesters and urging the security forces to show restraint.
Mark Toner, the US State Department spokesman, echoed that call, urging the security forces to "protect, not prevent, peaceful demonstrations."
Maduro, speaking at a meeting with high-ranking political and military officials, denounced that as a "green light (for) a coup."
The often fragmented opposition has been galvanized since last month's controversial Supreme Court ruling.
The court partly backtracked after an international outcry, but tension only increased when authorities slapped a political ban on opposition leader Henrique Capriles on April 7.
According to a recent poll, seven in 10 Venezuelans disapprove of Maduro, whose term does not end until 2019.