The Spanish giants, level on 65 points from 26 matches, pulled further away at the top as Barca defeated third-placed Valencia 3-0 at the Nou Camp and Real romped to a 4-1 victory at struggling Real Valladolid in the late kickoff.
Real, dumped out of the Champions League by Olympique Lyon in midweek, led champions Barca on goal difference and Valencia were 18 points back on 47.
Sevilla, who drew 1-1 with Deportivo La Coruna on Saturday, were fourth on 44.
After a draw and a defeat in their previous four La Liga matches, Barca needed a convincing performance at the Nou Camp to get their title defence back on course and again it was league top scorer Messi who made the difference.
The European champions found it difficult to exert their customary dominance in a goalless first half before Messi weaved through the Valencia defence in the 56th minute and fired a low shot past goalkeeper Cesar Sanchez.
Substitute Thierry Henry, who scored a hat-trick against Valencia last season, then set Messi up for his 21st and 22nd goals of the campaign.
The first came after he cut in from the right and curled the ball into the far corner and the second from a dinked effort that left Sanchez on the seat of his pants.
"Messi is the best player in the world and makes everything easier," assistant Barca coach Tito Vilanova, on the bench in place of the suspended Pep Guardiola, told a news conference.
SHATTERED DREAM
Real went top on goal difference last weekend after Barca were held 2-2 at Almeria but the club were rocked on Wednesday when Lyon shattered their dream of winning a 10th European title at their Bernabeu stadium in May.
A trademark Cristiano Ronaldo free-kick set them on their way in the 28th minute in Valladolid before Higuain scored his 17th, 18th and 19th goals of the campaign to go second behind Messi in the La Liga scoring charts.
A mistake from goalkeeper Iker Casillas gifted relegation-threatened Valladolid a goal in the 58th when the Spain captain's attempted clearance ricocheted into the net off Real defender Raul Albiol.
"We had to shake off a lot of pressure which had filtered into the dressing room," Real director general Jorge Valdano said in a television interview.
"But (Ronaldo's) goal made things easier and opened the way for the win," the Argentine added.
Barca and Valencia were both missing their leading strikers at the Nou Camp, with Zlatan Ibrahimovic suspended after his sending-off in Almeria and Spain international David Villa sidelined with a shoulder injury.
The best early chance fell to Valencia midfielder Jordi Alba in the fifth minute. Portuguese defender Miguel Monteira whipped over a cross and Alba's powerful header flashed narrowly over the crossbar.
After Messi put the home side ahead, Barca keeper Victor Valdes produced a superb stop to deny substitute Nikola Zigi
