In Washington, President Barack Obama, first lady Michelle Obama, Vice President Joe Biden and wife Jill Biden walked out to the White House's South Lawn for a moment of silence at 8:46am - the time the first plane struck the south tower in New York. Another jetliner struck the Pentagon at 9:37am.
"Our hearts still ache for the futures snatched away, the lives that might have been," Obama said.
A moment of silence was also held at the US Capitol.
In New York, loved ones milled around the memorial site, making rubbings of names, putting flowers by the names of victims and weeping, arm-in-arm. Former Gov. George Pataki, New Jersey Gov. Chris Christie and others were in attendance. As with last year, no politicians spoke. Mayor Michael Bloomberg watched the ceremony for his final time in office.
Carol Eckna recalled the contagious laugh of her son, Paul Robert Eckna, who was killed in the north tower.
"Just yesterday, you were 28," she said. "Today, you are 40. You are forever young. Dad and I are proud to be your parents."
The anniversary arrived amid changes at the Flight 93 National Memorial in Shanksville, where construction started this week on a new visitor centre. On Wednesday, the families of the passengers and crew aboard United Flight 93 recalled their loved ones as heroes for their unselfish and quick actions. The plane was hijacked with the likely goal of crashing it into the White House or Capitol, but passengers tried to overwhelm the attackers and the plane crashed into the field. All aboard died.
"In a period of 22 minutes, our loved ones made history," said Gordon Felt, president of the Families of Flight 93, whose brother, Edward, was a passenger.
Outside Washington, hundreds of people gathered for a short, simple ceremony at an Arlington County plaza 4.8 kilometres from the Pentagon. First responders from the county were among the first on the scene that day.
Fire Chief James Schwartz said ceremonies like Wednesday's - which featured an honour guard and a moment of silence- serve as a reminder of why first responders spend so much time preparing for disaster.
"I've often said this has been the fastest 12 years of my life," Schwartz said. "But if you are a surviving family member, I'd imagine this has been the longest 12 years of your life, because you're waking up every day with a hole in your heart."
Around the world, thousands of volunteers pledged to do good deeds, honouring an anniversary that was designated a National Day of Service and Remembrance in 2009.
By next year's anniversary, a 9/11 museum is expected to be open beneath the memorial plaza in New York City. While the memorial honours those killed, the museum is intended to present a broader picture, including the experiences of survivors and first responders.
"As things evolve in the future, the focus on the remembrance is going to stay sacrosanct," memorial President Joe Daniels said.
Douglas Hamatie, whose 31-year-old cousin Robert Horohoe worked for Cantor Fitzgerald and died on 9/11, drew applause from the crowd when he declared that the day should become a national holiday.
"The kids today, they know when the next iPhone's coming out, and they know when the next Justin Bieber concert is, but they don't know enough about 9/11," he said. "So let's change that, please."
The organisers have said they will always keep the focus on the families, and that was evident this year as relatives gathered on the tree-laden plaza, where a smaller crowd gathered - only friends and family of the victims were allowed.
Vicki Tureski, who lost her brother-in-law on September 11, said the victims' families will help each other through the years to come.
"Strangers who are now friends, friends who are now family, family who pull us to our feet each day," she said. "I promise to continue to keep you in my prayers as we go through decade two of carrying the tragedy of 9/11 with us."
- AP