A moment of silence was held ahead of the start before some 36,000 runners set off, 9,000 more than normal.
Officials have mounted a huge security operation that includes a ban on rucksacks and screening at checkpoints.
In last year's race two bombs exploded near the finish line, killing three people and wounding more than 260.
The BBC's Nick Bryant in Boston says that never before has the marathon been run amid so many layers of security, as 500,000 are expected to watch the activities.
'Very safe'At the scene
The rising sun first starts warming spectators on the same spot where the bombs exploded last year.
Today it is a popular spot. But many here chose the location as an act of defiance, and emotions are still high.
One woman said she broke into tears when she arrived.
And she expects more tears as the day moves on.
Athletes with disabilities were the first competitors to set off, at 08:50 local time (12:50 GMT).
The elite women's race started at 09:32, with the elite men setting off half an hour later, followed by thousands of other runners.
Protecting the 26.2-mile (42.2km) route has involved a massive mobilisation of law enforcement agencies, including police units, bomb squads and Swat teams from other states.
The Boston police department has erected 8,000 steel barricades, 1,200 more than last year.
Before the race, runner Katie O'Donnell, who competed in last year's race, said she could not imagine the range of emotions she would feel this year.
"I think I'm going to start crying at the starting line and I'm not sure I'll stop until I cross the finish line," she said.
Athletes with disabilities were the first to cross the starting line
The run-up to the event was dominated by tributes to the victims of the bombingMany people in the city have been wearing "Boston Strong" T-shirts.
Last year's winner of the men's elite race, Ethiopian Lelisa Desisa, is competing again and has met several victims of the blast.
He said the victims had given him inspiration: "We have to look to the future. There has to be a resilience. I am ready to win again."
Running duo Natalie Stavas and her father Joe recall last year's Boston marathon bombing
Bombing suspect Dzhokhar Tsarnaev, 20, is due to stand trial in November. He has pleaded not guilty to 30 charges, including 17 that carry the death penalty.
Prosecutors allege that he set off two pressure cooker bombs with his older brother Tamerlan, 26, who later died in a police shootout.
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