The world number four overcome the challenge of the Spaniard in four sets at Flushing Meadows, with Murray's three successes coming in breakers.
Despite admitting that he struggled to deal with Lopez's serve, the Brit revealed that he is "pleased" to have progressed.
"He played some really good stuff. He served especially well when he was down on serves. He was able to dictate the game and he has one of the best serves on Tour," Murray said during his post-match interview.
"I played well at the end of the tie-breaks and that was the difference. I'm pleased to have got through."