Nyquist has lived up to his favouritism to extend his unbeaten record in the 142nd Kentucky Derby at Churchill Downs, sparking talk of a second consecutive Triple Crown champion.

Nyquist took his record to eight wins with a smooth trip under Mario Gutierrez on Saturday (Sunday AEST)

Nyquist pulled away from Gun Runner down the straight and held off a closing charge by Exaggerator to win the first leg of US thoroughbred racing's Triple Crown series for three-year-olds.

Exaggerator, the second choice, finished second by 1-1/4 lengths followed by Gun Runner, who was 4-1/2 lengths off the pace.

"He's amazing," Gutierrez said.

"You get this two-year-old baby with thoughts of getting into the Kentucky Derby.

"Everything has translated into reality. There are no words for it."

Nyquist jumped cleanly from gate 13 and Gutierrez eased him back to allow speed runner Danzing Candy, to clear him from the outside.

After Danzing Candy dropped back in the later stages, Gun Runner took over the lead but at the top of the stretch, Nyquist blew past the colt and opened up a wide lead heading for the finish.

Exaggerator, who ran along the rail in the middle of the pack through the first half of the 1-1/4 mile (2000m) race, made a gallant charge down the stretch and closed within a length but could not overhaul the favourite.

It was a second Derby win for Gutierrez who teamed with Nyquist's trainer Doug O'Neill to win four years ago with I'll Have Another.

"He's such a special horse, you can see it in his eye on a daily basis," O'Neill said.

"He's such a professional. At any human sport he'd be the top notch athlete.

"He's just first class. Just the way he carries himself, he's the type of horse would be in the gym all day, go to bed early, he knows when to rest, he knows when to bring his A game.

"There is no way you could be nervous. You just knew he was going to figure out a way to pull it out at the end and he did."

The next leg of the Triple Crown, won for the first time in 37 years last season by American Pharoah, is the Preakness Stakes at Pimlico in Baltimore on May 21.