Mason Stajduhar finished with one save for Orlando City, who improved to 2-0-2 in four all-time encounters with FC Cincinnati. The Lions recorded a 3-0 win in the teams' first meeting this season on May 1.
Brenner scored in the 42nd minute for FC Cincinnati, who saw their winless stretch extend to eight matches (0-2-6) and their home winless streak reach seven (0-3-4).
FC Cincinnati goalkeeper Kenneth Vermeer made four saves before exiting the contest with an undisclosed injury. Przemyslaw Tyton came on in the 65th minute for his first action since that May 1 contest.
FC Cincinnati opened the scoring on Saturday for their first goal since Luciano Acosta tallied in a 1-1 draw against Atlanta United on July 21.
Alvaro Barreal sent a nifty diagonal feed across the box to Brenner, who unleashed a massive strike that sailed past a diving Stajduhar for his team co-leading fourth goal of the season.
Orlando City took advantage of an ill-advised back-heel kick by FC Cincinnati's Allan Cruz to set up the tying goal. Nani, who entered the contest as a substitute in the 55th minute, sent a shot from outside the box that handcuffed Vermeer for his team-leading ninth goal of the season.
Nani also scored in the first encounter against FC Cincinnati in May.
Vermeer prevented Orlando City from opening the scoring in the 28th minute after cutting down the angle and making a stop on Tesho Akindele.
FC Cincinnati nearly answered six minutes later as Acosta's shot from outside the box sailed just wide of the net.