The 21-year-old Briton, making his debut in the race, again proved untouchable when the peloton wound up for the final sprint, beating Jordi Meeus into second place while Magnus Cort Nielsen finished third.
Visma have now won seven stages in the race, with Brennan's five victories added to Wout van Aert's two, underlining their dominance of the Vuelta's flat and rolling stages.
Enzo Paleni, Sinuhe Fernandez and Fredrik Dversnes attacked shortly after the start of the 185-km stage, although Dversnes quickly dropped back. Paleni and Fernandez pressed on and built a lead of more than five minutes around the halfway mark.
Visma, driven for long spells by Steven Kruijswijk, kept the breakaway within reach, with Cofidis also contributing as they worked for Bryan Coquard.
A brief acceleration by Red Bull-Bora-Hansgrohe split the bunch inside the final 50 kilometres, but the peloton soon regrouped. Paleni and Fernandez still held a lead of 1:50 with 25 kilometres remaining before Fernandez took the intermediate sprint at San Jose de la Rinconada.
Paleni then attacked alone with 15 kilometres left, but his lead shrank rapidly, and he was caught inside the final three kilometres.
UAE, NetCompany Ineos and Uno-X all tried to shape the run-in, but Brennan timed his effort best to seal another emphatic win.
Overall leader Enric Mas finished safely in the bunch to retain the red jersey for a ninth successive stage, leading Felix Gall by 2:06 and Primoz Roglic by 2:10.