Carles Puyol's howler gifted the visitors an equaliser after Argentina forward Messi had put Barca ahead in the 17th minute before Bojan Krkic and substitute Pedro netted with clinical second-half strikes.
Messi grabbed a fourth in added time at a rain-lashed Nou Camp when he controlled a Daniel Alves pass and lifted the ball over Tenerife goalkeeper Sergio Aragoneses for his 31st league goal of the campaign.
With two matches left, Barca have a La Liga record 93 points, four clear of second-placed Real Madrid, who have a game in hand and can cut the gap back to one with a win at Champions League hopefuls Real Mallorca on Wednesday.
Barca's points total from 36 matches surpasses the 92 accumulated by Real under Fabio Capello in the 1996-97 season when there were 22 teams rather than 20.
"We have 93 points and I don't even believe it myself," coach Pep Guardiola said at a news conference.
"We will have to win in Sevilla if we want to be champions," the 39-year-old added. "It's the 17th consecutive match that we have played with a gap of only three or four days. The effort is incredible."
Barca's final two games are away to fifth-placed Sevilla and home to relegation-threatened Real Valladolid, while Real play Athletic Bilbao, who are fighting for a Europa League spot, at home and struggling Malaga away.
SLICK SURFACE
Guardiola's side, with only the league to fight for after last week's Champions League exit, took early control on a slick surface and Brazil right back Alves fluffed one good chance before providing the cross that led to Messi's opener.
Swedish striker Zlatan Ibrahimovic nodded the ball into the World Player of the Year's path and he chipped a delicate shot from close range that evaded desperate lunges by Aragoneses and defender Pablo Sicilia.
Messi came close to a second with a curled shot in the 22nd minute before captain Puyol squandered posesssion and Daniel Kome sent Roman Martinez clear to score with a neat finish past Barca keeper Victor Valdes six minutes before halftime.
Alves released Bojan to score with an angled drive in the 63rd and Pedro, who replaced injured Spain centre back Gerard Pique at the break, ran on to Messi's deflected pass to score a third that ricocheted in off Aragoneses.
Alves conjured another assist in the 93rd minute, Messi bringing the ball down with his left foot and finishing neatly with his right.
World Cup-bound Spain forward Juan Mata scored twice and international team mate David Silva netted one as third-placed Valencia came from behind to beat bottom side Xerez 3-1 at the Mestalla in the late kickoff.
Victory for Unai Emery's side all but guarantees them an automatic spot in next season's Champions League, while defeat for Xerez leaves them needing a miracle to avoid being relegated on their debut in Spain's top flight.
Villarreal's slim hopes of a Champions League spot were killed off when defender Mateo Mucacchio was dismissed in the 16th minute and they lost 4-2 at Almeria.
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