"The Europe that we know is too weak, too slow, too inefficient," he said as he began the closely-watched address at the prestigious Sorbonne university in Paris.
"But Europe alone can give us the ability to act in the world faced with big contemporary challenges."
Macron's proposals for a post-Brexit shake-up include plans to give the 19-member eurozone a finance minister, budget and parliament, as well as creating a Europe-wide "rapid reaction force" to work with national armies.
He even raised the prospect of major changes to the Common Agricultural Policy, the EU's giant farm subsidy programme, which has historically been defended by France and its powerful agricultural lobbies.
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Macron is desperate for German Chancellor Angela Merkel's endorsement of his reform agenda, but his plans were dealt a blow by shock election results that saw the anti-immigration, eurosceptic Alternative for Germany (AfD) emerge as the country's third-largest party.
Macron appeared to respond to FDP chief Christian Lindner directly today, saying: "I don't have red lines, I only have horizons."
Macron used the Sorbonne speech to argue the case for institutional changes, initiatives to promote the EU, and new ventures in the technology, defence and energy sectors.
Along with Brexit and the German elections, Macron's proposals are likely to top the agenda at a two-day summit of all 28 EU members in Estonia from Thursday.
Over the next few months, analysts say they expect Merkel will try to form a coalition led by her conservative CDU/CSU with the pro-business FDP and the ecologist Greens.
French officials considered that now was the best time to intervene in the German debate, before a coalition contract is drawn up between the different parties setting out their roadmap for the four-year term.