Mayer outpointed former world champion Jennifer Han by unanimous decision (100-90, 100-90 and 99-91) to retain her WBO and IBF junior lightweight world titles in Costa Mesa, California.
It was the third title defence for Mayer (17-0, 5 KOs), and her first as a unified world champion. She did everything but force the stoppage, outlanding Han by a more than 3-1 clip (192-63).
Early in the fight, Mayer busted open Han's nose with a right hand and used a stiff jab to keep Han on the defensive.
Han (18-5-1, 1 KO) landed the occasional counter against the ropes, but Mayer was never threatened. It's onwards and upwards for the woman ranked No. 5 on ESPN.com's pound-for-pound rankings.
Mayer said, "I feel like I did a lot of good things in there. Her movement, I think, is what she does best and it throws you off. She gets her spacing in a little bit, so I had to throw her off and stay behind the jab. Coach Al [Mitchell] reminded me to stay behind the jab, set the right hand up.
"She would duck sometimes and make me miss. I started to go to the body. All in all, she's a tough, durable girl. That's why we chose her for this fight. We knew she would push me, but I feel like I did well.
"I wanted to get the stoppage I feel like I hurt her in the eighth round, almost finished her. This is another reason why I'm advocating for three-minute rounds.
"I've been pretty clear that I want to go undisputed at 130. [Alycia] Baumgardner and [Hyun Mi] Choi, I've been calling them out. I want [either] fight, but if they're not going to give me that fight in a timely fashion, I'm game to go up and challenge the winner of [Amanda] Serrano versus Katie Taylor."
Elsewhere , Giovani Santillan extended his record to 29-0 with a seventh-round stoppage of Jeovanis Barraza.
Santillan is a welterweight contender to watch after he laid a savage beating on Colombian veteran Barraza in the evening's co-feature. An accumulation of punishment prompted referee Thomas Taylor top stop the fight, as Santillan outlanded Barraza 193-37. Santillan, who is trained by Robert Garcia, picked up his first stoppage since 2019.
Santillan said, "I am humbled by the support of my hometown, San Diego. Once again, they came out in force. They motivate me to do my best every time out there.
"I am going to keep working to earn a welterweight world title shot. I have a great team behind me, and when the time comes, I'll be ready."