The crowd was booing and security came to boot the woman out, but Nadal — who has a famously meticulous routine — was able to see the funny side and kept on laughing.
There was plenty of speculation on social media the woman may enjoyed a few beverages before the match, giving her some liquid courage to go through with her brazen stunt.
"No," Nadal laughed after the match when asked if he knew the woman, who was sitting in front of a Spanish flag. "And honestly I don't want to know."
The world No. 2 has been struggling with tightness in his lower back since arriving in Australia last month, but showed few signs of it with the roof closed on Rod Laver Arena.
He will next play Britain's Cameron Norrie in his quest for a 21st grand slam title.
"I always try to be better, sometimes it happens and sometimes not. Tonight has been a positive evening for me, winning in straight sets," he said.
"For me, I am now just focusing on what is coming because that is going to be more difficult."
The writing was on the wall, with Nadal enjoying a perfect record against qualifiers at the Australian Open, where he has reached the round of 32 every time he has played, barring his shock first round exit in 2016.
Nadal sent Serb Laslo Djere packing with little drama in the opening round and it was a similar story with Mmoh, whose father Tony twice played at the Australian Open.
After getting his measure in the first few games, Nadal pounced to break in the fourth and never looked back, racing through the set in 27 minutes.
While serving big, the American lacked accuracy and was mercilessly punished by a player ranked 175 places above him.
The 2009 champion, who has a history of back problems, is bidding to win his 21st major title and claim sole ownership of the men's major record, which he currently shares with Roger Federer.
But the king of clay has often laboured in vain on Melbourne's hardcourts, reaching five finals but only having the one title, falling in the quarter-finals last year to Dominic Thiem.