The top-seeded Scot received a wild card into the event after world No. 2 Novak Djokovic withdrew last week because of personal reasons. Murray got pushed in his first tournament since losing to Rafael Nadal in the Wimbledon semifinals.
Smyczek, a 22-year-old from Milwaukee ranked 192nd in the world, notched his first ATP Tour win with a straight-sets victory in the first round. He hung in early in the third set against the world's fourth-ranked player when there were breaks in the first three games before Murray took control with Barry Bonds watching.
"I hope to have a good run here," Murray said. "There were a lot of long rallies in the first and second sets. Hopefully, it will stand me in good stead."
Lopez will play wild card James Blake, who outlasted Benjamin Becker 7-5, 7-6 (5) at the Los Angeles Tennis Center on the UCLA campus, with Boston Celtics star Kevin Garnett looking on. Blake, a finalist here in 2007, improved to 3-0 against the German.
Blake rallied from a 2-4 deficit to win the first set. He blew two match points in the 10th game of the second set before closing out the match 7-5 in the tiebreak.
"It definitely could've gone the other way easily," he said. "I'm doing a good job of not letting anything rattle me."
Blake reached his first quarterfinal since February in Delray Beach, Fla. The 30-year-old lost time because of a right knee injury earlier this year and he lost in the first round of his three previous tournaments. He has yet to make a semifinal this year.
"Knee pain is barely there. It's great," he said, a bag of ice taped to his knee as a post-match precaution. "When you hit 30, it becomes very apparent that your career is finite. I feel great about being healthy and playing well."
Lopez won his hard-court season debut, having been idle since reaching the round of 32 at Wimbledon.
Falla had lost in the first round of his three previous tournaments, including to Roger Federer at Wimbledon. The left-hander, ranked 65th in the world, advanced to his third quarterfinal of the year.
"I'm really happy because I won a tough match," he said. "I fought a lot. I was tired, too. We were running a lot. We played long rallies."
Gulbis was playing his first tournament in two months after sustaining a hamstring injury in a first-round loss at the French Open. He was clearly rusty and easily irritated by fans who yelled during his service motion.
"It was really tough for me to go long rallies," he said. "I physically couldn't run anymore. I couldn't make any winners. Basically, nothing worked. If you don't fish for two months, maybe you're bad at fishing."
He received a point penalty for smashing his racket and criticized the referee afterward. By his tally, Gulbis broke two rackets, although he tossed others.
"His only fun in life is to give warnings. It's like police," he said. "Whatever I would do I would get warning."