The defending champion lost the opening set 6-1 in just 26 minutes and failed to recover from that point as he dropped the next two sets to his Bulgarian opponent 7-6(4) 6-2.
Upon exiting his home Grand Slam, a defeated Murray told BBC Sport: "I'm very disappointed with the way I started. I felt that gave him confidence at the beginning. It's a lot easier to settle down when you're two sets up. It wasn't a great day.
"I felt fine in the warm-up but got off to a bad start, that was the disappointing part. It wasn't good enough. There is time to come back, but I didn't take my opportunity in the second set. He played a very solid match, making few mistakes and a lot of returns. All the percentages were in his favour. I just wish I'd made it tougher for him."
Murray last missed out on a place in the semi-finals at SW19 back in 2008.