"We should build in the American continent something similar to what was the economic community that was the beginning of the current European Union," he added, emphasising the need to respect the sovereignty of the region's mostly Spanish-speaking nations.
The summit's kickoff focused attention on the region's center-left leaders, including Peru's new president, Pedro Castillo, Cuba's Miguel Diaz-Canel and Venezuela's Nicolas Maduro.
No representative of Brazil's right-wing president Jair Bolsonaro attended.
But some fissures emerged, including criticism from Uruguay's center-right president Luis Lacalle, who said his participation in the summit should not be interpreted as an embrace of some of the region's more authoritarian regimes.
The leaders gathered at the invitation of Lopez Obrador with a stated aim of weakening the Washington-based OAS, the long-standing regional body that excludes Cuba and is viewed with skepticism by many of Latin America's center-left leaders.
In his remarks, Bolivian president Luis Arce called for a global agreement to lower debts for poor countries while Cuba's Diaz-Canel spoke out for an end to the US trade embargo against the communist-run island.
Venezuela's late president Hugo Chavez helped set up CELAC in 2011, and his embattled successor Maduro arrived in the Mexican capital late on Friday in a surprise addition to the assembled heads of state.