The true test, he said, was in how people respond in times of difficulty, when their efforts to make the world better run into resistance.
While the fate of the very unpopular legislation known as the Affordable Care Act remains unsure, Obama opened a window during the speech into his ideal health care arrangement. After the 30th, they will need 60 votes to pass reform, an impossible task given Democrats' universal opposition.
Opponents of the Obama-era health law to expand coverage for more Americans have assailed it as costly and ineffective.
Obama acknowledged "it frustrates" to have "to mobilize every couple of months" to beat back repeal efforts, but rallied his supporters to mobilize against it. They also say people shouldn't be forced to buy health insurance.
"Even if at the current moment the federal government is not as engaged in these efforts as I would like, nevertheless, progress continues because of the efforts of people like Bill [Gates] and a whole host of entrepreneurs and universities and cities and states", Obama said.
As he has largely done since leaving office, Obama did not mention Trump by name, but he made it clear that he disagreed with the president's viewpoint.
But the response to setbacks, Obama said, has to be "to reject cynicism and reject pessimism and push forward".
Participants at the September 20 event have shared data and innovative solutions to ensure progress continues and the ambitious targets of the Sustainable Development Goals (or Global Goals) are met. Partnerships focusing on women's empowerment, digital financial inclusion and community health workers will be announced as "Accelerators" and tasked with speeding up progress to achieve the goals.
For years until its final event last year, the most well-known of the corollary events was the Clinton Global Initiative, created by former President Bill Clinton as a way to raise attention and money for causes worldwide. The speakers included Clinton and a raft of business and political leaders.