Murray and the Spaniard battled to a tense 7-6 (8-6) 5-7 10-5 victory against Joe Salisbury and Rajeev Ram in front of a packed crowd.
The win carried major significance for Murray, who broke down in tears at January's Australian Open when revealing he may never play tennis again.
The Briton underwent major hip surgery shortly after but responded well and returned to tennis at Queen's ahead of next month's grand slam at Wimbledon.
He hailed Lopez for his form throughout the week - his partner having also won the singles crown - before saying, to huge cheers, that he had been in "no pain" throughout the event.
"He [Lopez] was brilliant. There's nothing else to say," Murray said.
"It was an amazing win [from Feliciano] in the singles and even at the end of the match there, he came up with some brilliant returns and serves.
"I really enjoyed it. I felt very relaxed at the beginning of the week and was getting more nervous as the week went on and my competitive instincts kicked in.
"My hip felt great, no pain. I'll try to keep progressing from here but I'm just happy being back on the court."
Murray and Lopez were broken in the seventh game of the match and, as a result, they looked like losing the opener.
But, serving for the set, Salisbury and Ram were broken, eventually forcing a tie-break which their opponents claimed.
There was just one break in the second set, as Murray and Lopez, serving to stay in the set at 5-6, faltered.
A match tie-break followed, the race to 10 being won easily.
Lopez acknowledged his day was extraordinary before adding how pleased he was to see Murray back on court.
"This happens only once in a lifetime to win here at singles and doubles," he said.
"I'm so happy to have this man playing with me. We're so happy that you're back on a tennis court.