Under the watchful eye of riot police, more than 2,000 supporters of the Movement for Democratic Change (MDC) carried anti-Mugabe placards and sang party songs before their leader Morgan Tsvangirai gave a speech attacking Mugabe's rule.
Anti-government protests in Zimbabwe have often been brutally broken up by police under the authoritarian regime of the president, who has been in power since independence in 1980.
Mugabe, 92, remains active but his increasingly fragile health has sparked intense speculation over his successor and the fate of the country when his rule come to an end.
"Mugabe has no solution to the crisis," Tsvangirai said in a brief speech to supporters gathered in Africa Unity Square wearing T-shirts in the party's red colours.
"We are here to tell Mugabe and his regime that you have failed.
"We are not demanding an overthrow of the government... We are demanding a dignified exit for the tired Mugabe.
"It's time Mugabe listens to the voice of the people. The people shall liberate themselves."
"This is a demonstration against poverty and corruption," Douglas Mwonzora, an MDC party spokesman told journalists.
"We have an empty promise of 2.2 million jobs which are not there. We have massive corruption."
The MDC has vowed to hold more protests around the country, which is also beset by severe food shortages worsened by its economic decline since land reforms started in 2000.
"Old clueless Mugabe must go," read one protest placard, while another said "Enough" in Zimbabwe's three main languages.
Mugabe, who still gives fiery 90-minutes speeches on his feet, is expected to stand again for election in 2018.
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