Running just two weeks before his 39th birthday, he had the names of the 2013 bombing victims on his bib.
"At the end, I just kept thinking, 'Boston Strong. Boston Strong,'" he said. "I was thinking give everything you have. If you get beat, that's it."
Keflezighi completed the 26.2 miles from Hopkinton to the finish on Boylston Street in Boston's Back Bay on Monday in a personal-best 2 hours, 8 minutes, 37 seconds. He held off Kenya's Wilson Chebet, who finished 11 seconds behind.
Photos: 2014 Boston Marathon
Keflezighi went out early and built a big lead. But he was looking over his shoulder several times as Chebet closed the gap over the final two miles. After realizing he wouldn't be caught, Keflezighi raised his sunglasses, began pumping his right fist and made the sign of the cross. He broke into tears after crossing the finish line, then draped himself in the American flag.
No U.S. runner had won the race since Lisa Larsen-Weidenbach took the women's title in 1985; the last American man to win was Greg Meyer in 1983. Meyer and Keflezighi embraced after the race.
"I'm blessed to be an American and God bless America and God Bless Boston for this special day," Keflezighi said.
Rita Jeptoo of Kenya successfully defended the women's title she said she could not enjoy a year ago. Jeptoo finished in a course-record 2 hours, 18 minutes, 57 seconds. She is a three-time Boston Marathon champion, having also won in 2006.
"I came here to support the people in Boston and show them that we are here together," she said. "I decided to support them and show them we are here together."
Jeptoo broke away from a group of five runners at the 23-mile mark. Buzunesh Deba of Ethiopia finished second in 2:19:59. Countrywoman Mare Dibaba was third at 2:19:52. All three women came in under the previous course record.
American Shalane Flanagan, who went to high school in nearby Marblehead, Mass., finished seventh after leading for more than half the race. She gambled by setting the early pace, but fell back on the Newton Hills about 21 miles into the race.
"It does mean a lot to be that my city was proud of me," she said. "I'm proud of how I ran. I don't wish I was it was easier. I wish I was better."
After breaking a 27-year American drought at the New York marathon, Keflezighi contemplated retiring after the 2012 NYC Marathon. But that race was canceled because of Superstorm Sandy, and he pulled out of the Boston Marathon in April because of injury.
He was the first American to win a medal in an Olympic marathon since Frank Shorter won gold in 1972 and silver in 1976. His 2009 New York victory broke a 27-year American drought there.
Another American, Tatyana McFadden, celebrated her 25th birthday Monday by winning the women's wheelchair race for the second straight year. She was timed in in 1 hour, 35 minutes, 6 seconds.
McFadden was born in Russia and lived in an orphanage as a child before starring at the University of Illinois. She also won the 2013 NYC Marathon women's wheelchair race after taking the titles in Boston, London and Chicago last year.
Ernst van Dyk of South Africa won the men's wheelchair division for a record 10th time. The 41-year-old crossed the finish line in 1 hour, 20 minutes, 36 seconds.
Van Dyk holds the record for most all-categories Boston Marathon wins. This was his first win at this race since 2010.
Marathon officials said 35,755 runners registered for the race, with 32,408 unofficial starters. The field included just less than 5,000 runners who did not finish last year and accepted invitations to return this year.
BACK IN BOSTON: Jeff Bauman, who lost his legs in the bombing, stood in the stands just past the finish line with his fiancee, Erin Hurley, and fellow amputee Adrianne Haslet-Davis. They were applauding runners as they crossed.
Bauman was wearing his prosthetics and had the help of two crutches. The group sat a few feet away from Carlos Arredondo, who helped save his life.
It was the first time Bauman had returned to the finish line area since the attacks.
"It feels great" to be back, he said. "I feel very safe."
— Michelle R. Smith and Steve Peoples
LIVE FROM THE COURSE: Bill Kole, AP's New England bureau chief, is running the race — and tweeting from every mile. He reports: "Mile 17: Sign of the race: 'Dad, I'm pregnant.' And right before the dreaded Newton hills. Dang, dad."
— Bill Kole — https://twitter.com/billkole
IN THEIR HONOR: Meb Keflezighi, who gave the Boston fans their first American men's champ in more than three decades, wore the names of four victims on his running bib. Written in marker in small, neat letters in each corner were Krystle, Lingzi, Martin and Sean.
Krystle Campbell, Lu Lingzi and Martin Richard were killed in the bombings during last year's race. MIT Officer Sean Collier was killed days later in the hunt for the bombing suspects.
— Steve Peoples — https://twitter.com/sppeoples
RETURN TO FENWAY: Boston Marathon survivor Marc Fucarile is back at Fenway Park four days after marrying his longtime fiancee there.
The 35-year-old native of Stoneham, Mass., threw out the ceremonial first pitch before the Red Sox's traditional morning game on Patriots' Day.
Fucarile lost his right leg in last year's bombings and walked with a prosthetic and a cane to the mound before the game against the Baltimore Orioles.
Then he handed his cane to a companion, wound up and threw to former Red Sox outfielder Kevin Millar. The pitch reached Millar on a fly, going high into the left-handed batters' box.
On Thursday, Fucarile married Jennifer Regan at Fenway. They had delayed their wedding while he recovered from serious injuries. Fucarile was the last bombing victim to be discharged from Massachusetts General Hospital.
— Howard Ulman — https://twitter.com/hbulman
US CHAMP: Meb Keflezighi won the men's race, giving Boston its long-hoped-for American champion a year after the bombings.
No U.S. runner had won the race since Lisa Larsen-Weidenbach took the women's title in 1985; the last American man to win was Greg Meyer in 1983.
The 38-year-old from San Diego looked over his shoulder several times over the final mile. After realizing he wouldn't be caught, he raised his sunglasses, began pumping his right fist and made the sign of the cross.
JEPTOO REPEATS: Rita Jeptoo of Kenya successfully defended the title she said she could not enjoy a year ago after the fatal bombings.
Jeptoo finished Monday's race in a course-record 2 hours, 18 minutes, 57 seconds. She becomes the seventh three-time Boston Marathon champion.
— Pat Eaton-Robb — https://twitter.com/peatonrobb
HOW HEARTBREAK GOT ITS NAME: Heartbreak Hill, the pinnacle of a series of hills that stretch about 4 miles through Newton, lives up to its name. After 16 mostly hilly miles, sore and tired thighs must now propel a racer up, up, up. It sure gets the heart pumping and can drain the best runner.
But it wasn't a physical blow that gave it its name.
During the 1936 race, hometown hero Johnny Kelley was looking for a repeat when he tangled with Ellison "Tarzan" Brown. Catching the Rhode Island phenom in the hills, Kelley patted his rival on the shoulder as he passed him on the final climb. But instead of discouraging Brown, it fired him up, and he passed Kelley. By the time they sailed past Boston College, Kelley was done. Boston Globe sportswriter Jerry Nason the next day described the defeat as "breaking Kelley's heart."
— Rik Stevens — https://twitter.com/RikStevensAP
SECURE AREA: For all the talk of enhanced security, there were no metal detectors at some security checkpoints around the finish line Monday morning, nor were security guards patting down people or checking their pockets as they entered the secured area around where last year's bombing took place.
Such pat downs are common at large gatherings such as professional sporting events or concerts.
Security guards along the finish line focused instead on those carrying bags, which were searched before people were allowed to enter the fenced perimeter.
— Steve Peoples — https://twitter.com/sppeoples
SCREAM TUNNEL: As waves of runners pass by, the noise from Wellesley College students has escalated and fans are going wild, rattling cowbells. One holds a sign that has a slot for a young woman's face, calling it a "kissing booth." Freshman Ashley De La Russo wipes sweat off her face after getting a big smooch from one runner who she says was pretty cute. "The energy here is amazing," said De La Russo, from Orlando, Fla. "I knew it was going to be a scream tunnel, but this is just unbelievable."
— Paige Sutherland — https://twitter.com/psutherland458
WAVING FLAGS: Carlos Arredondo and his wife, Melida, are standing in the viewing stands just past the finish line waving small American flags. Arredondo was wearing his trademark cowboy hat and a Boston Strong shirt.
The two were at last year's race, handing out flags, when the bombs went off.
Arredondo quickly ran to the aid of Jeff Bauman and helped rush him in a wheelchair to medical attention, a scene captured in an arresting AP photo. Bauman lost his legs.
— Michelle R. Smith — www.twitter.com/MRSmithAP
PLAY BALL: The local baseball team has its traditional Patriots' Day morning start time Monday. Instead of wearing "Red Sox" across the chests of their home uniforms, the players' jerseys read "Boston," just as they did for the tribute to bombing victims at Fenway Park last April 20.
The reigning world champs host the Baltimore Orioles with the first pitch at 11:05 a.m.
PARTY ON: Once out of the starting town of Hopkinton, security appeared no stiffer than in past years. The traditional party atmosphere was in full force.
Loud music blared from a pair of tree-mounted speakers. Up the road, a string band played. Fans hauled coolers, beach chairs, strollers, even grills to the yards and driveways along the course.
The wall of sound that is Wellesley College was in full throat, with hundreds of students screaming loudly enough to be heard a quarter of a mile away.
— Rik Stevens — https://twitter.com/RikStevensAP