On the evening that he became Barcelona's joint second-highest appearance-maker, Messi stole the show again to ensure that Ernesto Valverde's side took full advantage of Atletico Madrid's defeat on Saturday.
The Argentine maestro broke the deadlock after 18 minutes with a pinpoint free kick into the top corner and then doubled the lead right at the end of the first half after latching on to Luis Suarez's back-heel.
Suarez got his own name on the scoresheet shortly after the hour mark, while Loren Moron pulled a goal back for Betis late on, but the night belonged to Messi and he capped off a majestic individual performance with the pick of the bunch five minutes from time, lobbing the keeper with an exquisite first-time finish.
The result sees Barca take another giant stride towards defending their La Liga crown and keeps them firmly on course for a potential treble this season.
Betis more than matched the league leaders for much of the first half and could have taken the lead after just 13 minutes when Joaquin's diagonal ball was turned back into the area by Cristian Tello, but Jese Rodriguez could not get the required contact on it in the middle when a better finish would have left Marc-Andre ter Stegen little chance.
All that separated the two teams in the opening 45 minutes were moments of individual magic, and Messi provided the first of those with a stunning free kick after 18 minutes, leaving Pau Lopez no chance despite shooting at the goalkeeper's side.
The Argentine almost repeated the trick when Barcelona won another free kick in a similar position seven minutes later, and again Messi got it on target but this time Lopez got across to make the save on the opposite side.
Betis were looking every bit as threatening as their visitors, though, and it took some fine last-ditch defending from Barcelona to keep them at bay shortly before the half-hour mark as they peppered the box with dangerous crosses.
Jese was the next to come close for the hosts when he drilled a low strike narrowly wide of the far post after good work from Tello down the left.
Barca hit back in the end-to-end contest, though, and they should have doubled their lead five minutes before the interval when Messi laid the ball into the path of an unmarked Suarez, whose finish was tame and easy for Lopez to collect.
Suarez may not have been able to make the most of Messi's pass on that occasion, but the roles were reversed in the final action of the first half as Barcelona doubled their lead through Messi's second.
The Argentine fed the ball into the feet of Suarez, who found him again with a brilliant back-heel and Messi steered his finish past the keeper to put Barcelona in complete control at the interval.
Suarez looked to pick up where Messi left off at the start of the second half when he slammed an effort into the side-netting, but the Uruguayan appeared to be having an off night in front of goal and squandered another glorious chance on the hour mark when he rounded the keeper but could not squeeze the ball home from a tight angle.
Moments later he put an even better chance wide of the far post when he was bearing down on goal with only the keeper to beat and no defenders in sight, but it proved to be third time lucky as the former Liverpool man finally scored with his third gilt-edged opportunity in as many minutes.
The goal came from arguably his most difficult chance of the lot too as he dribbled his way through three Betis defenders, leaving them in a heap behind him before slotting his finish into the bottom corner.
Suarez should have had more too, but he again failed to connect with a shot properly when presented with another chance inside the area 16 minutes from time as Barcelona went in search of a fourth.
It was Betis that got the game's fourth goal, though, as Jordi Alba failed to deal with a low cross from the left and Diego Lainez teed up Loren, who curled his finish past Ter Stegen and into the top corner.
Barcelona almost restored their three-goal lead immediately when Arturo Vidal's curling effort was tipped over by Pau Lopez, but the visitors would not have to wait long for another goal and this time the keeper could get nowhere near another moment of pure Messi brilliance.
The ball was dropped back to the five-time Ballon d'Or winner just inside the box, and he produced a perfect first-time lob over Lopez, who was no more than two yards off his line but could only watch as the ball clipped the underside of the crossbar and went in.
It was a goal which took Messi level with Cristiano Ronaldo on 34 La Liga hat-tricks, and the quality of his individual performance was such that even the Betis fans stood up and chanted his name to recognise a genius at work.
Messi was not done there, though, and he came within inches of a fourth goal with the final action of the match when he poked the ball against the inside of the post and watched it bounce across the line and out.
The Argentine still took the matchball home as Barcelona opened up a 10-point lead over their closest challengers with only 10 games of the season remaining, surely putting them on course for a fourth league title in five years.
REAL BETIS (3-1-4-2): Lopez; Mandi, Bartra, Sidnei; William (Moron 75'); Joaquin (Emerson 67'), Sanales, Guardado, Tello; Lo Celso (Lainez 68'), Jese
BARCELONA (4-4-2): Ter Stegen; Roberto, Pique, Lenglet, Alba; Rakitic (Alena 88'), Busquets, Arthur (Semedo 64'), Vidal; Suarez (Coutinho 90'), Messi