Typically, the 6-year-old mare started the 1 1/4-mile race dead last in a field of 12. Jockey Mike Smith didn't ask her to pick it up until Zenyatta neared the stretch turn. She then ran by everyone -- except Blame. At the end, Zenyatta was gaining with every one of her giant strides but ran out of ground, losing by a head.
Fly Down caught Lookin At Lucky in the shadow of the wire to finish third.
Blame, picked by many as the biggest threat to Zenyatta's quest for a 20-for-20 lifetime record, finished in 2:02.28. He picked up his fourth win in five starts this year, losing only to Haynesfield in his last race, the Jockey Club Gold Cup.
Blame's jockey, Garrett Gomez, said he thought in deep stretch he was home free.
"I thought I was going to get there pretty easily because I hadn't seen her (Zenyatta)," Gomez said. "Then I caught her out of the corner of my eye."
Winning trainer Al Stall Jr. said he felt fortunate that yearlong plans to get Blame into the race worked out. "A whole lot of things all came together at once," he said.
A distraught Smith, near tears after the race, said Zenyatta was uncomfortable early in the race with dirt hitting her in the face. Then he couldn't move as quickly as he would have liked because a wall of horses in front of him would have forced Zenyatta too wide.
Still, Smith shouldered the blame for the loss. "It's my fault," he said. "She just had too much to do."
"I just wish I would have been in the race a little earlier," Smith said. "The outcome would have been different. It was a gallant effort on her part. She made up a lot of ground. It's pretty hard to swallow."
Trainer John Shirreffs and owner Jerry Moss were more philosophical.
"I'm just so happy with everything Zenyatta's done," Shirreffs said. "She ran her heart out today. She ran a great race." Asked how he will handle the loss, he added, "This is the first time this has happened. What are you going to do? It's horse racing."
Moss, co-founder of A&M Records, added, "She lost to a really good horse and we're proud of her. She ran a really great race."
The outcome certainly will ignite a debate over which of the two top Classic finishers should be Horse of the Year. Zenyatta won last year's Classic at Santa Anita but lost yearend honors to the now-retired Rachel Alexandra.
Celebrity Breakups and divorces of 2014 [PHOTOS]