Lionel Messi scored on his 500th Barcelona appearance as Luis Enrique's side finished a magnificent 2015 on top of the La Liga table.
Heiko Westermann's own-goal - after Neymar's controversial penalty had hit the bar - gave Barca the lead.
Messi recovered from a knock which forced him to go off for treatment to double the lead before Luis Suarez scored twice after the interval.
Barca finish 2015 with 180 goals in all competitions, a Spanish record.
They are level on points with Atletico Madrid, who won 2-0 at Rayo Vallecano, but have a game in hand over their title rivals.
Real Madrid, 3-1 winners over Real Sociedad , are two points behind in third.
Betis formed a guard of honour before kick-off as Barca walked out to have a photograph with their five trophies of 2015 - the Champions League, La Liga, Copa del Rey, Uefa Super Cup and Fifa Club World Cup.
Barca took the lead when Messi was harshly judged to have been fouled by keeper Antonio Adan and, although Neymar slipped and hit the crossbar with his spot-kick, Westermann directed the rebound into the back of his own net.
Messi slid home his 425th goal for the club after 34 minutes to add to their lead.
Suarez scored twice after the break to take over from Neymar as La Liga's leading scorer with 15.
Barca were denied by the woodwork four times after the interval as they produced an attacking master-class.
They start 2016 with an away game at 13th-placed Espanyol on 2 January.
Betis lost Westermann and Bruno Gonzalez to injury, while boss Pep Mel was sent to the stand for arguing.
LINEUP, BOOKINGS (4) & SUBSTITUTIONS (6)
Barcelona
- 13 Bravo
- 06 Dani Alves Booked
- 14 Mascherano
- 23 Vermaelen
- 24 Mathieu (Adriano - 67' )
- 04 Rakitic
- 05 Busquets (Bartra - 57' )
- 20 Sergi (El Haddadi - 86' )
- 10 Messi
- 09 Suárez
- 11 Neymar
Substitutes
- 01 ter Stegen
- 03 Piqué
- 08 Iniesta
- 15 Bartra
- 17 El Haddadi
- 18 Alba
- 21 Adriano
Real Betis
- 13 Adán Booked
- 02 Molinero
- 04 González Cabrera (Pezzella - 17' Booked )
- 17 Westermann (Digard - 36' )
- 11 Vargas
- 16 Cejudo
- 25 dos Santos Araujo Booked
- 18 N'Diaye
- 10 Ceballos Fernández
- 09 van Wolfswinkel
- 24 Castro (van der Vaart - 75' )
Substitutes
- 01 Giménez
- 07 Joaquín
- 12 Piccini
- 15 Digard
- 20 Pezzella
- 22 Portillo
- 23 van der Vaart
Ref: Iñaki Vicandi Garrido
Att: 83,630
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