Orb gave jockey Joel Rosario and trainer Shug McCaughey their first victory in the Kentucky Derby with an emphatic performance at Churchill Downs.
The Malibu Moon colt took his 100% record this year to four when coming from way off a strong pace set by Palace Malice.
The field were well strung out in the wet conditions and Rosario, who won the Dubai World Cup on Animal Kingdom at Meydan five weeks ago, kept his cool to bring Orb with a telling run on the turn for home.
Despite being brought wide for his challenge, Orb headed leader Normandy Invasion inside the final furlong and pulled away to score by two and a half lengths from Golden Soul.
Revolutionary was a length back in third with Normandy Invasion just behind in fourth.
"I dreamed of winning this race with this horse" - Shug McCaughey
"It means everything to me. I've always dreamed of this day," McGaughey told NBC Sports.
"Around the quarter pole I thought he might win and then when they left the eighth pole he looked like he might pull himself up but Joel did a good job when he knew the other horses were coming. At the 16th pole we had it done.
"I dreamed of winning this race with this horse, but didn't think it would happen until he won the Florida Derby."
Rosario said: "It's awesome. Winning the Dubai World Cup and now this, it's like I'm having a dream.
"He was relaxed in the race and did exactly what I wanted. I had a perfect trip."
The Aidan O'Brien-trained Lines Of Battle under Ryan Moore was seventh but was never able to threaten the leaders.