First-half goals from Neymar and Pedro put the Catalan giants on the way to all three points before a brace from Cesc Fabregas after the break completed their scoring.
Betis did manage to get on the scoresheet when Jorge Molina slotted home from the penalty spot in stoppage time but it was nothing more than a consolation.
The only downside for Barcelona was Lionel Messi's first half departure due to a leg injury and he looks set to miss Argentina's forthcoming friendlies with Ecuador and Bosnia and Herzegovina.
Earlier, second-placed Atletico Madrid squandered a chance to briefly go ahead of Barcelona as they drew 1-1 at Villarreal in a game of two own goals.
Although Los Rojiblancos dropped points for only the second time this season, they could not complain about the result, and were in fact the weaker side from start to finish.
They took a fortuitous lead with just two minutes gone when Villarreal full-back Mario Gaspar headed into his own net, but late in the second half the Yellow Submarines, who remain fourth in the league table, got the goal their efforts deserved when Juanfran turned the ball into the wrong goal.
Valencia had to come from behind twice to earn a 2-2 draw at home to Real Valladolid but will consider it two points lost after dominating possession and creating the better chances, as well as missing an early penalty.
Ever Banega skied a spot-kick after five minutes and Javier Guerra then gave the visitors the lead against the run of play.
Dorlan Pabon equalised for Valencia just before the half-hour mark but Gilberto Alcaraz put Valladolid ahead again early in the second half.
Sophiane Feghouli equalised on 76 minutes and Pabon had a chance to win it, but in the end Valencia were grateful to goalkeeper Vicente Guaita, who made two saves late in the game to allow his side to cling on to a point.
Sevilla halted a two-match losing streak with an impressive 3-1 victory at 10-man Espanyol to move above the struggling Catalan club in the table.
Los Rojiblancos had suffered back-to-back defeats against Real Madrid and Celta Vigo in recent weeks but made an ideal start at the Estadi Cornella-El Prat as Federico Fazio and Machin Vitolo put them two goals to the good inside the first 10 minutes.
The home side's captain Sergio Garcia pulled one back midway through the first half but Carlos Bacca restored Sevilla's two-goal lead and it proved decisive.
Ronaldo's treble was his second in succession at the Bernabeu, having also struck three in the recent 7-3 victory over Sevilla.
The Portugal international wrapped up his latest three-goal haul with strikes in the 12th, 27th and 76th minutes to take his league tally to 16 for the campaign.
The 28-year-old also set up Madrid's second for Karim Benzema in the 18th minute while Gareth Bale's pass helped Sami Khedira make it 4-0 in the 36th minute.
Sociedad pulled a 61st-minute goal back through Antoine Griezmann.
Goals from two half-time substitutes saw Athletic Bilbao battle back for a well-deserved 2-1 win over Levante.
The hosts trailed to David Barral's 33rd-minute strike but came good inside the final 20 minutes as first Mikel Rico popped up to level before Aritz Aduriz nodded in the winner six minutes from the end.
Aduriz, who along with Rico was introduced by coach Ernesto Valverde at the interval, failed to complete the match after receiving a straight red card for a late clash with Aloys Nong.
Getafe were held to a 1-1 draw at home to Elche as they failed to hold on to a first-half lead despite the best efforts of goalkeeper Miguel Moya.
Pedro Leon netted his fourth goal of the season midway through the first half before the Primera Division newcomers struck back to claim just their second point from the last four matches.
Moya was tested in both halves but was unable to keep out Richmond Boakye's leveller after 61 minutes.
Rayo Vallecano halted a run of three successive defeats with a 2-0 win at fellow strugglers Celta Vigo which also lifted Paco Jemez's side off the foot of the Primera Division.
Goals from Jonathan Viera and Joaquin Larrivey stopped the rot for the visitors and they now join their opponents on 12 points just above the bottom three.
On Friday, Youssef El Arabi netted a second-half hat-trick as Granada recorded a 3-1 victory over Malaga .
The home side were on top for the majority of the game but neither team could break the deadlock in a goalless first half.
El Arabi scored after 48, 59 and 77 minutes and Juanmi Jimenez's equaliser after the first only levelled matters up for four minutes before El Arabi handed his side the lead again.
A solitary goal by Rodri guided Almeria to their third successive La Liga victory and ensured Osasuna remained firmly mired in trouble at the bottom of the table.
On-loan Barcelona B striker Rodri pounced after Andres Fernandez fumbled Sebastian Dubarbier's corner in the 18th minute.
It means Osasuna now have just one win in five games and could find themselves bottom of the table at the end of the weekend.
For Almeria though, Friday's victory continued their good run after they had found themselves at the wrong end of the standings following five successive defeats.