Los Blancos entered the match off the back of four successive draws in all competitions, but four goals in the first period sent them on their way to all three points, which has taken them level with Atletico Madrid at the summit and two points ahead of champions Barcelona, who are down in fourth.
The visitors then had a golden chance to score a second moments later when Isco delivered a cross onto the boot of Cristiano Ronaldo, but the Portuguese, who netted five times during the recent international break, somehow missed the target from close range under little pressure.
Another opportunity came and went for Real Madrid in the 14th minute when Bale sent a diving header towards the bottom corner, only to be denied by a reaction save from former Los Blancos stopper Antonio Adan.
Betis's first sight of the Real Madrid goal arrived in the 20th minute when the club's record goalscorer Ruben Castro found a yard of space outside the box before having a pop, but his effort was always moving away from goal.
Ronaldo and Marcelo both tested Adan as the first period continued to gather pace, but Betis were a threat on the counter-attack as Joaquin and Castro continued to see plenty of the ball in dangerous positions.
Real Madrid scored their second of the match in the 31st minute, however, when Kroos robbed Joaquin of possession before feeding Karim Benzema and the Frenchman simply placed the ball past Adan.
Two became three in the 40th minute when Benzema's deflected shot fell to Marcelo, who spun inside the Betis box before striking the ball into the ground and finding a route past Adan to all but secure the points in the first period.
It got worse for Betis in the final minute of the first half, however, when a beautiful team goal ended with Ronaldo sliding a pass in to Bale and the Welshman set the ball back to Isco, who finished off their fourth goal.
Betis, who made a double change at the interval as Alvaro Cejudo and Roman Zozulya replaced Alex Alegria and Darko Brasanac, came close to their first of the night early in the second period when German Pezzella cut the ball back to Joaquin inside the box, but the Spaniard's header was cleared by Pepe.
Joaquin again came close moments later with a low strike from a wide angle, but the ball flew wide of the post during what was an end-to-end period of the match, with Ronaldo still intent on getting his name on the scoresheet.
Betis deservedly gave their supporters something to cheer in the 55th minute when Cejudo collected a clever lay-off from Joaquin before slipping the ball past Keylor Navas following some sloppy defending from the away side.
Real Madrid restored their four-goal advantage in the 63rd minute, however, when Isco found space in a wide position before curling a stunning effort into the top corner for his second goal of the night.
Benzema should have joined Isco on two goals in the 71st minute when he was put through by Kroos, but Adan was on hand to make a stunning save and Ronaldo's frustration continued as he headed over the crossbar moments later.
Ronaldo finally had his goal in the 78th minute, though, when the 31-year-old burst through the Betis defence before firing the ball past Adan as he ended a run of three league games without a goal.
Next up for Real Madrid is a Champions League group game against Legia Warsaw on Tuesday night, before returning to league action at home to Athletic Bilbao next Sunday. Betis, meanwhile, will travel to Osasuna in the league on Friday night in what is a key fixture for Poyet.