Murray, who had a slow start to the hardcourt season with a third round loss in Montreal last week, arrived in Cincinnati eager to get in matches ahead of the August 26-Sept 9 U.S. Open, where he will arrive as a defending grand slam champion for the first time.
The Cincinnati hardcourts, where the 26-year-old Scot has twice been crowned champion, proved a perfect spot to build some momentum and Youzhny the perfect opponent as the Wimbledon champion ran his record to 4-0 against the Russian.
On a sunny morning on the outskirts of Cincinnati, Murray got off to a bright start, twice breaking Youzhny to storm into a 4-0 lead before wrapping up the first set in 34 minutes.
Murray broke his 31-year-old opponent again to open the second and, with the exception of a small hiccup when Youzhny broke at 4-2, rolled into the third round and a meeting with Frenchman Julien Benneteau.
"I had good anticipation so I was able to chase a lot of balls down and today I managed to get a lot of balls back," said Murray, winner of four titles this season.
"It's not necessarily getting to the ball it's putting it in a position where it's difficult for your opponent to hit a winner off and I think I did that well today."
Murray's match was the start of spectacular day of action on centre court at the Western and Southern Open, which brings together the top players from the ATP and WTA Tours in a joint event that for many will serve as a final tune-up to the year's final grand slam.
World number one's Novak Djokovic and Serena Williams followed Murray on an action-packed morning schedule while Rafa Nadal will feature in the night session.
In other morning matches, 11th seeded German Tommy Haas cruised to a 6-4 6-1 win over Spain's Marcel Granollers.
