None of Venezuela's opposition leaders was invited to the ceremony.
"More than ever, Venezuela will not be a "yankee" colony, nor a colony of anyone. The time for our true independence has come, 200 years on", Chavez said.
'Democratic socialism' lauded
Chavez, wearing the trademark red beret of his army paratrooper years, reiterated his accusations of US government meddling in Latin America while praising Venezuela's move towards "democratic socialism".
"The moment has come for us to reach true sovereignty and independence" in the region, he said.
Chavez laid a wreath on the tomb of Simon Bolivar, the independence fighter, in a ceremony at the National Pantheon in Caracas.
Bolivar went on to liberate a string of South American nations from Spanish colonial rule after declaring Venezuela a free and sovereign state.
Chavez worships Bolivar and even renamed his country the Bolivarian Republic of Venezuela after he took power in 1999.
The celebrations commemorated April 19, 1810, when the municipal council of Caracas first led a successful movement to depose the Spanish governor.
Venezuela finally achieved independence on June 24, 1821.
Later at night, Chavez hosted a summit of the Bolivarian Alternative for the Nations of Our America, or Alba - a left-leaning bloc aimed at boosting Latin American integration and countering US influence.
At this meeting, Chavez gave warning that Colombia would become a serious threat to its neighbours if Juan Manuel Santos, the favourite in polls to succeed Alvaro Uribe, wins the presidential election.
"This is a threat to all of us, especially for Ecuador, Venezuela and Nicaragua," Chavez said.
He cited Santos' record as defence minister including a controversial military strike against Colombian leftist Farc guerrillas in Ecuadorean territory in 2008.
"These people feel they have the support of the Yankees," he said, alluding to recent comments by Santos about the need to keep "terrorists" at bay.
For their part, Venezuelan opposition groups - gathered under the political coalition Table of Democratic Unity (MUD) - said that Chavez's 11-year rule had "promoted separation and confrontation" in Venezuelan society.
Chavez "has systematically reduced our democratic abilities, and compromised our future and our progress", the coalition said in a statement on Sunday.
Carlos Andres Perez, a former Venezuelan president, similarly questioned whether it was time to rejoice over independence when a "militarised and authoritarian regime" was in power, referring to Chavez, a former military commander.
In more than a decade of tumultuous rule, Chavez has nationalised public utilities, vital industries and media outlets and launched health and education programmes for the poor.
He has also intensified pressure on opposition groups and dissidents.