The Lobos are now 14-3 overall and 5-2 in conference matches while the Rebels improved to 10-6 overall and 5-1 in MW play.
It was New Mexico's first time losing before the fifth set this season and just the second home loss (other vs. then-No. 19 Colorado State on Sept. 28).
The Rebels used a balanced attack and offspeed shots tipped over UNM's blockers to defeat the Lobos.
"We knew they would do that," head coach Jeff Nelson said of the over-the-block attacks. "They like to go short serve, they like to go short on attacks -- all of it was in the game plan, all of it was in the film we watched. Our kids didn't committ to the game plan tonight. UNLV outworked us on our home floor."
Four UNLV players hit for double-digits in kills: Sekola Falemaka (13), Julia Topor (12), Katlin Winters (11) and Madeline Westman (10).
The Lobos were also outblocked by UNLV, 12-7.
"They're a bigger team than us and we decided to try to overpower them," Nelson said. "We didn't play smart, we didn't stay focused on the things we knew that would work.
"It was also probably our poorest passing effort of the year. We probably passed six or seven balls in the last few games that were likely out of bounds. UNLV played a great match and we didn't committ to the things that we needed to in order to be successful."
Redshirt sophomore Hannah Johnson recorded her 11th double-double with 47 assists and 16 digs.
New Mexico heads to California next week for a pair of Mountain West matches, stopping first at Fresno State on Nov. 17 and then at San José State on Nov. 19.
The Lobos next home match and only other home match of the month is Oct. 26, against Nevada at 1 p.m. MT. It will be the team's Dig Pink night.