Oxbow won the Preakness on Saturday ruining Orb's bid, as the favorite, to capture the Triple Crown.
Thoroughbred racing will have to wait at least another year for its first Triple Crown champion since Affirmed in 1978.
Oxbow led from start to finish. It was the sixth Preakness victory for Hall of Fame trainer D. Wayne Lukas and 15th Triple Crown win, the most in horse racing history.
"I get paid to spoil dreams," Wane Lukas said to NBC immediately after the race.
“It’s so special,” Oxbow's Hall of Fame jockey Gary Stevens said after the race. “We were flying under the radar after the derby and didn’t get a lot of respect even with the great performance...We came in here with a lot of confidence."
Oxbow ran the 1 3/16th miles Preakness in 1:57:54 and had 15 to 1 odds of winning the race. Oxbow was sixth in the Kentucky Derby. He went off as a 15-1 underdog and paid $32.80, $12 and $8.80.
Orb, and his Dominican jockey Joel Rosario, finished fourth. The Kentucky Derby winner was a 3-5 favorite in Saturday's race, but he became another casualty of starting on the rail in the Preakness. Since 1950, only two horses have won the middle jewel of the Triple Crown from the No. 1 post position.
“I thought we were in a good position, the pace was slower than I really anticipated," Orb's owner Stuart Janney said. "I’m disappointed and I’ll probably be more disappointed tomorrow than I am today."
Orb's five-race winning streak ended on an overcast, windy day at Pimlico Race Course. The brown colt had not lost since Nov. 24.Orb extended his winning streak to five with a thrilling victory in the Derby two weeks ago, when jockey Rosario patiently guided the colt from 17th to first in the final half mile over a sloppy track.
Rosario had said he didn't think the inside start on the rail "would be a problem" for Orb.
"Thought we were going to be fine," Rosario said after the race. "Once I passed half a mile he had a hard time to keep going. When I passed the half mile, I worried a little about it."
As for the Triple Crown? Eleven horses have done it, 19 failed and three others did not run in the Belmont.
Itsmyluckyday finished second and paid $7.80 and $5. Mylute paid $5.20 to show. Mylute, with Rosie Napravnik in the saddle, came in fifth in the Kentucky Derby. Racing at the track where she earned her first career victory, Napravnik was attempting to become the first female jockey to win the Preakness.
The Associated Press contributed to this report.