The American broke to lead 2-0 in the first set and saved seven break points in the next game. In the second set, Nishikori saved three break points at 1-1 but hit a forehand volley long to lose his serve in the ninth game.
"Felt pretty good," said the 13th-seeded Querrey. "I thought I served really well and ... moved well. I was pretty happy for my first grass-court match of the season."
He didn't face another break point after the third game of the first set.
"Yeah, that was a big game," Querrey said. "He had six or seven break points, and fortunately I hit big serves on four or five of them and played the other ones tough. I think that was a huge game."
Young saved five of six break points and broke twice to take the opening set, and broke in the opening game of the decider.
Last year's semifinalist Feliciano Lopez of Spain beat Dmitry Tursunov of Russia 7-6 (4), 6-3 to set up a second-round match with Andy Roddick. The American is a four-time champion at Queen's Club and is returning to action after missing the French Open because of a shoulder injury.
Lopez stunned Rafael Nadal in the quarterfinals here last year, and again showed good grass-court form by hitting 18 aces and losing serve just once.
The top-ranked Nadal, who won his sixth French Open title on Sunday, is among eight players with byes into the second round.