Los Blancos struggled to get going and created few chances in the first half, aside from Karim Benzema rattling the post after Francis Guerrero failed to clear his lines.
At the other end, Marc Bartra forced a save out of Keylor Navas from distance, and the Costa Rican had to be alert to tip over a superb lob from Giovani Lo Celso after he raced onto a ball between Nacho and Marcelo from Junior Firpo.
Pau Lopez denied Vinicius Jr. from a tight angle after the break, but the hosts otherwise rarely troubled the visitors.
Loren Moron broke the deadlock with a deserved opener for Betis when he rifled home Andres Guardado's cross in the 61st minute.
Former Los Blancos player Jese Rodriguez scored a second in the 75th from Firpo's cutback to ensure Madrid ended their campaign with 12 defeats in La Liga.
Zidane Wrong to Put Faith in Marcelo
According to Marca's Santiago Siguero, Madrid boss Zinedine Zidane wants Marcelo to remain at the club this summer amid links with Juventus, as he still considers the Brazilian to be one of Real's "most valuable assets."
While it's understandable the Frenchman might want to show faith in those who were key to his success during his first spell, Marcelo's performance on Sunday was indicative of his poor season.
The left-back was a frequent liability at the back, and Betis repeatedly left him exposed.
The visitors capitalised on Marcelo's failure to track back with Loren's opener, as Guardado picked him out unmarked with the defender nowhere to be seen.
Marcelo relied on Raphael Varane to bail him out at times, and at one point he even needed Luka Modric to track back to cover him, as ESPN FC's Dermot Corrigan observed:
His contributions at the other end were found wanting too, as he misplaced passes in the final third during his forays upfield.
Marcelo may have only just turned 31 on May 12, but he has been in serious decline this season—he had been the best left-back in the world for much of his career, but he's no longer close to that.
He has been left out of Brazil's Copa America squad this summer for a reason, and Real need to be similarly ruthless with those failing to live up to their billing.
A departure this summer could help fund Real's much-needed rebuild too, so Zidane should reconsider putting his faith in Marcelo next season.