Murray wrapped up the first set in just 26 minutes, breaking Lopez twice. The Spanish left-hander offered up more resistance in the second set, but Murray made his breakthrough in the ninth game to assume a two-set lead. He then raced through the third set with two more service breaks to claim victory in one hour and 54 minutes.
"[Today] was better," Murray said. "The conditions were tough to start. But after having a long match the other day it was good to be done quickly in a night match. I enjoy playing guys who come to net against me. He's not an easy guy to play against, but he does make a lot of errors at times."
The 24-year-old Murray won his eighth straight match as he improved to a 37-10 match record on the season. The Dunblane native came into the US Open on the back of winning his 18th ATP World Tour title in Cincinnati (d. Djokovic) and was also victorious at The Queen's Club (d. Tsonga) in June.
Murray reached at least the semi-finals in all three of the first Grand Slams of the year, going on to finish runner-up at the Australian Open (l. to Djokovic). Next up in his quest to win his first major title, Murray will face Donald Young, whom he lost to in Indian Wells in March.
"[Young] can hit winners from all parts of the court," assessed Murray. "He comes forward and volleys well. He's very flashy and can get on a roll."
No. 12 seed Gilles Simon put paid to Juan Martin del Potro's US Open comeback as he defeated the 2009 champion 4-6, 7-6(5), 6-2, 7-6(3) in the third round at Flushing Meadows.
Former World No. 4 del Potro was unable to defend his US Open crown last year after being sidelined for all but three tournaments due to a right wrist injury. He returned to action at the start of the 2011 season and has captured two ATP World Tour titles en route to lifting his ranking from World No. 258 to No. 18.
The Argentine had his chances to push Simon to a fifth set. After recovering from a break down at 2-3 in the fourth set, del Potro then had three set points at 4-5, 0/40 on Simon's serve, but was unable to convert. The Frenchman was to offer up no more opportunities and took advantage of wayward forehands from del Potro in the ensuing tie-break to claim victory in just under four hours.
The 26-year-old Simon is through the last 16 of a major for the second time this season, having also reached that stage at Roland Garros (l. to Soderling). He came into the US Open on a run of good form, winning his ninth ATP World Tour title in Hamburg (d. Almagro) and reaching the quarter-finals in Cincinnati (l. to Murray).
Simon is bidding to reach a Grand Slam quarter-final for the second time, having reached the last eight at the 2009 Australian Open (l. to Nadal), and goes on to face American No. 28 seed John Isner.