Accompanied by wife Meghan Markle, the Duke of Sussex launched a thinly-veiled swipe at the Supreme Court's Roe vs Wade ruling that handed abortion rights back to individual US states.
He claimed it represents a "global assault on democracy and freedom" as he also hit out at Russia's invasion of Ukraine.
Harry said: "This has been a painful year in a painful decade. We are living through a pandemic that continues to ravage communities in every corner of the globe.
"Climate change wreaking havoc on our planet with most vulnerable suffering most of all. The few weaponising lies and disinformation at the expense of the many.
"And from the horrific war in Ukraine to the rolling back of constitutional rights in the US we are witnessing a global assault on democracy and freedom – the cause of Mandela's life."
A protester taking a stand against Meghan and Harry's appearance
SHANNON STAPLETON
But Harry and Meghan's appearance in New York for Nelson Mandela Day backfired spectacularly as protesters lined the streets outside.
Prince Harry addresses the United Nations General Assembly
EDUARDO MUNOZ
One placard read: "Mandela spent 27 years behind bars in SA.
"Markle spent 18 months in castles and complained on TV during a pandemic.
"Why are they here?"
The appearance marks the first time the couple have been seen in public since jetting to the UK to celebrate the Queen's Platinum Jubilee last month.
Meghan and Harry in New York
SHANNON STAPLETON
It has not been well received, with former MEP Martin Daubney describing Harry as a "platinum-plated plonker" on GB News.
Republican politicians were also quick to condemn the Duke of Sussex's comments.
US Rep Buddy Carter said: "The US is protecting the lives of unborn children. Russia is killing innocent Ukrainians.
"We are not the same and comparing the two is sick and perverse.
"I would remind Prince Harry that spreading disinformation is incredibly damaging to the 'democracy and freedom' he is so concerned about."
Rep Lisa McClain added: "Yet again, the Duke and Duchess are sticking their nose into American politics by attacking the US rule of law.
"I think it's time we buy them a history book on the Revolutionary War to remind them that our government stopped caring about the 'royals' opinion back in 1776."