Cristiano Ronaldo continued his fantastic week after lifting the Ballon d’Or on Monday with a thumping long-range drive to open the scoring before Gareth Bale silenced his recent critics with a trademark free-kick to make it 2-0.
Karim Benzema then notched his 100th goal for Madrid in first-half stoppage time as he blasted home after classy play from Luka Modric.
Angel di Maria made it four just after the hour mark with another stunning effort from distance and Alvaro Morata rounded off the scoring in stoppage time.
All three leading clubs are now tied on 50 points, but Barca and Atletico can move back in front when then face Levante and Sevilla respectively on Sunday.
Bale had struggled since his return from a calf injury at the beginning of the year with coach Carlo Ancelotti even admitting on Friday that the Welshman could do better.
But the Italian praised the former Spurs man’s display as his side produced their best display of the year to date.
“Bale played well, as did the whole team. We played with great quality and concentration throughout the game,” he said.
“Everything went well and therefore we have to be happy.
“It was an important opportunity for us to go to the top of the table and we can sleep well tonight.”
It was once again Ronaldo who stole the show early on as he opened the scoring 10 minutes in with a thunderous drive from 25 yards out that flew into the top left-hand corner of Stephan Andersen’s net.
Ronaldo nearly had another memorable goal to add to his collection 10 minutes later as he skipped past two Betis defenders before firing across the face of the goal.
The visitors didn’t have to wait long to double their advantage, though, as Bale did make his mark with a dipping free-kick on 25 minutes that beat the stationary Andersen, although the Danish keeper should have done better.
Ruben Castro missed a wonderful opportunity to pull a goal back for the hosts when he failed to connect with Leo Baptistao’s fine low cross six minutes before half-time.
Instead, it was Madrid who struck again before the break as Modric continued his fantastic form of late with a wonderful piece of composed play inside the box to tee up Benzema to fire home at the near post.
Andersen redeemed himself somewhat at the start of the second period as he made a fine low save to his right to prevent Ronaldo doubling his tally and also turned away a fiercely struck effort from Benzema.
However, there was nothing the Betis keeper could do to prevent Di Maria making it four as he arrowed a low left-footed drive from 30 yards into the bottom corner.
And Betis’s afternoon was summed up in stoppage time when Morata nipped in to prod past Andersen as the home defence appealed in vain for offside.