The Argentinian took his goals tally to 60 for the season after coming on as a substitute with his side being held 2-2 by the spirited visitors and facing a real threat to their 13-month unbeaten home record in La Liga.
While the Catalan faithful revelled in Messi's display, his 35-minute cameo did little to dispel the growing - if unfair - theory that Barca are a one-man team.
Certainly the hosts looked shaky before his introduction, with Betis twice taking the lead through Dorlan Pabon and Ruben Perez.
Alexis Sanchez hit Barcelona's first equaliser while David Villa's 56th-minute header for 2-2 was his final contribution before he was immediately hauled off for Messi.
Within minutes Messi curled home a wonderful free-kick to hand his side the lead for the first time and leave many in the Nou Camp shaking their heads in disbelief.
But Messi was not finished there and moments later was applying the finish to a sublime team move that secured the points and means Barcelona can be crowned champions before they next kick a ball in anger should nearest challengers Real Madrid fail to beat Malaga on Wednesday and Espanyol next Saturday.
Messi's hamstring problem meant he was an unused substitute as Barcelona crumbled to a 7-0 aggregate defeat to Bayern Munich in the Champions League semi-final in midweek, and fans who turned up expecting a response this evening were left frustrated as Betis took the game to the hosts in the opening period.
The visitors took the lead with two minutes gone as Alex Martinez headed the ball on and Pabon had a simple task to tuck the ball home.
The hosts responded in the ninth minute when Andres Iniesta crossed for Sanchez to nod in from six yards, but it remained a disjointed display by the home side and their fans grew increasingly restless as the half wore on.
Villa twice forced Adrian into saves but the closest the hosts came to taking the lead was a Cristian Tello shot in the 41st minute that crashed down off the bar but was correctly ruled not to have crossed the line.
Given their place inside the top seven, Betis' display should not perhaps have been a surprise and they duly re-took the lead moments before the interval when Perez, on loan from Atletico Madrid, struck his first senior goal with a blistering effort from 30 yards.
Tito Vilanova's men needed an early response after the restart and got it 11 minutes in when Villa headed home a Dani Alves cross, but by that point Messi was already stripped and ready and Villa was withdrawn immediately.
And it took just 180 seconds for Messi to take the game by the scruff of the neck, the forward curling home a quite brilliant free-kick into the top-right corner from 25 yards to extend his scoring streak in La Liga to 21 games.
And with 19 minutes left Iniesta's backheel found Sanchez and his low ball across the face of goal was inch-perfect for Messi to tuck home an easy finish.
A hat-trick appeared on the cards and the Nou Camp rose to acclaim the feat in the final seconds as Messi ran through the Betis defence, but his lack of match fitness was evident in a tired finish that the goalkeeper had no problem keeping at bay.