Macron was greeted with a three-minute standing ovation even before he spoke and several others during his speech.
After reeling off a series of cultural references, ranging from Chateaubriand to jazz, he hailed a "very special relationship" between the two countries.
But he went on to warn that "the core our Western values themselves are at risk" and insisted that "democracy remains the best answer to the questions and doubts that are raised today".
"We are living in a time of anger and fear," he declared but, quoting former US president Franklin D Roosevelt's inaugural speech, went on to add "the only thing we have to fear is fear itself."
Much of the speech could be read as criticism of Trump.
Macron warned of the dangers of "extreme nationalism", spoke out against trade wars and called for the US to return to backing the 2015 Paris climate change accord.
Opposing isolationism and nationalism, he called for "a 21st-century world order based on a new breed of multilateralism", he said "we have to shape our common answers to the global threats we are facing".
"This requires more than ever the United States' involvement," Macron argued, a rebuff to Trump's isolationism.
Trade wars and global warming
Defending the market economy, he criticised growing inequality and warned of the dangers of trade wars, an implicit criticism of Trump's tariffs on steel and aluminium imports.
Macron has lobbied for the continuation of Europe's exemption from the tariffs during his visit.
Turning to climate change, a question on which Trump is publicly sceptical, Macron declared "Let us face it, there is no Planet B."
"I'm sure one day the United States will come back and join the Paris agreement," the French president said, referring to Trump's withdrawal from the accord.
Iran nuclear deal
He went on to defend his proposal to "broaden" the Iran nuclear deal, which Trump has threatened to "rip up".
"Iran should never possess nuclear weapons," he said. "Not now, not in five years, not in 10 years. Never." But he called for respect for its sovereignty and the avoidance of "past mistakes".
The Iran nuclear deal was signed on the initiative of the United States and "we should not abandon it without having something more substantial instead".
Macron raised the hope for an end to the Syrian conflict, repeating his call for the question to be introduced into a revised deal with Iran, and paid tribute to American and French soldiers who have died in the Middle East.
"What we love is in danger and together we have no choice but to prevail," he concluded to roars of applause and another ovation.