Sent off at 9-2 odds, Always Dreaming made it the fifth straight year that a Derby favorite has won, the longest such stretch since the 1970s.
Always Dreaming was followed across the finish line by a pair of longshots: 33-1 Lookin At Lee and 40-1 Battle of Midway.
Always Dreaming ran 1 ¼ miles in 2:03.59 and paid $11.40, $7.20 and $5.80.
Lookin At Lee returned $26.60 and $18.20, while Battle of Midway was another five lengths back in third and paid $20.80 to show.
Pletcher won his first Derby in 2010 with Super Saver; Velazquez won the following year with Animal Kingdom.
Classic Empire finished fourth, followed by Practical Joke, Tapwrit, Gunnevera, McCraken, Gormley and Irish War Cry. Hence was 11th, followed by Untrapped, Girvin, one-eyed Patch, J Boys Echo, Sonneteer, Fast And Accurate, Irap, and State of Honor.
Pletcher also trains Tapwrit and Patch.
Thunder Snow, the Dubai-based entry, didn’t finish. He broke poorly out of the starting gate and began bucking. He was caught by the outrider and he walked back to the barn on his own.