Madrid captain Ramos again showed nerves of steel to chip into the net from the spot after a VAR review for a handball by Betis defender Marc Bartra, who appeared to have been pushed by Madrid forward Borja Mayoral.
Earlier in the second half, Betis defender Emerson was given a straight red card for a foul on Luka Jovic following a VAR review, while Madrid's equalising goal, given as an own goal by Emerson, was awarded after another VAR intervention ruled Karim Benzema had been onside in the build-up.
Uruguayan midfielder Federico Valverde had given the champions the lead in the 14th minute with a finish from close range after fine work by Benzema by the byline. But Betis struck twice in quick succession through Aissa Mandi and William Carvalho to take a 2-1 lead at halftime.
"When you are up against Real Madrid and VAR it is too much," Betis boss Manuel Pellegrini angrily told a news conference after the match.
"We were much better than Real Madrid in the first half, we scored two goals and had three clear chances to score. The second half was more equal, then there was the red card, the penalty, and playing so much time with a man down was tough.
"When you are playing against Real Madrid and you concede a penalty and get a man sent off because of VAR it is very difficult. But I value how well we played when it was 11 against 11."
Madrid manager Zinedine Zidane added it wasn't his place to comment on VAR after the game.
"There's a referee there and he looks at the plays. In the end it's fair what happened. He's in charge. I never get involved with referees and I won't today. The important thing is the game we played, we gave everything on the pitch, a difficult match against a team that won their first two games, and we can be happy with the job done, they're three important points," he said.
And Ramos added that VAR interventions don't always benefit Real Madrid.
"I'd have to see them again, I was a long way away and I can't judge. From what I've been told it was a clear penalty. It can't change now. Sometimes they help us, sometimes they hurt us, referees are there to do the best job possible," he said.
Information from ESPN Correspondent Alex Kirkland was used in this report.