The Indianapolis Colts kicked off the annual draft party that filled three balconies at the venerable Manhattan theatre with fans decked out in their team colours by taking Luck, the celebrated Stanford quarterback, with the No. 1 pick.
After the Washington Redskins followed, as expected, by selecting Griffin, the Heisman Trophy-winning quarterback from Baylor, a string of four trades shook up the first half of the proceedings as teams jockeyed into position to nab the players they coveted.
Four more trades, including two made by the New England Patriots to move up, highlighted the second half of the draft, which is the lifeblood by which NFL teams restock their teams and address weaknesses.
The top of the draft offered no suspense as Luck and Griffin went one-two as undisputed top of the 2012 draft class.
Luck, considered one of the most polished quarterback prospects in recent years, will be taking over the reins of the Colts' offense from four-time NFL Most Valuable Player Peyton Manning.
"Yeah, Peyton Manning, arguably the greatest ever," Luck said about the 11-time Pro Bowler, who signed a five-year, $96 million deal to play with the Denver Broncos after the Colts decided to embark on a rebuilding plan.
"He was my football hero growing up. I realize you don't really replace a guy like that. Those shoes to fill are huge.
"If one day I can be mentioned alongside Peyton in quarterback history, it would be a football dream come true."
Luck was handed a No. 12 Indianapolis jersey, to match the uniform number he wore at Stanford.
"That's the number I'm wearing this year and hopefully for many years to come," said Luck, a drop-back passer who completed 67 per cent of his passes at Stanford, throwing for 82 touchdowns and 22 interceptions in compiling a 31-7 record as a starter.
Griffin, popularly known as RG3, is a running threat as well as a strong-armed passer and edged out Luck as winner of the Heisman in December as the top U.S. college player.
The Redskins so coveted Griffin, they traded their No. 6 overall pick along with a second-rounder this season and No. 1 picks in 2013 and 2014 to the St. Louis Rams in order to move up to No. 2 in the draft so they could claim him.
"I don't look at it as any added pressure," Griffin said.
"If anything, it makes me want to go out and get to work even sooner. They believe in me."
After the selection of those two blue chip quarterbacks, who will be linked as quarterbacking headliners of the 2012 draft, a flurry of trades followed.
The Cleveland Browns swapped picks with the Minnesota Vikings to take Alabama running back Trent Richardson with the third pick.
Minnesota, enriched by added picks in the fourth, fifth and seventh rounds, took offensive tackle Matt Kalil of Southern California.
The Tampa Bay Buccaneers traded the fifth pick to the Jacksonville Jaguars, who selected Oklahoma State wide receiver Justin Blackmon.
The Dallas Cowboys jumped to the sixth spot after a trade with St. Louis and took Louisiana State defensive back Morris Claiborne.
Moving up three places after a swap with the Seattle Seahawks, the Philadelphia Eagles took Fletcher Cox, a defensive tackle from Mississippi State, with the 12th pick.
Capping off the three-hour-long opening round with teams picking in reverse order of their 2011 records, the Super Bowl champion New York Giants took running back David Wilson of Virginia Tech.
The second and third rounds of the draft will be held on Friday, with rounds four through seven conducted on Saturday.