Sevilla welcomed Barca having won their last six league outings but never looked like maintaining that run as Ronald Koeman's side left with a 2-0 win.
Messi teed up Ousmane Dembele for the opener just before the half-hour mark with both sides having goals chalked out for offside.
The Barcelona skipper would then wrap up the victory with a scrappy effort five minutes from the end of a fairly routine afternoon's work.
Bottom club Huesca missed the chance to lift themselves out of the relegation zone as they conceded a late leveller in a 1-1 draw at fellow strugglers Eibar.
Sandro Ramirez scored for the visitors with less than 10 minutes remaining but they could not hold on as Papakouli Diop secured a share of the spoils for Eibar.
Alaves remain just a point above the bottom three after losing 1-0 at home to Osasuna, with Kike Barja grabbing the only goal of the game.
England international Jadon Sancho matched Messi's efforts as he chalked up a goal and assist in Borussia Dortmund's 3-0 win over Bielfeld.
Sancho picked up his 50th Bundesliga assist as he squared for Mahmoud Dahoud to open the scoring before converting from the penalty spot after Marco Reus had been fouled with Reinier Jesus going on to add the gloss late on.
Stuttgart also enjoyed a big win over rock bottom Schalke with Wataru Endo hitting two in a 5-1 romp.
Endo set the hosts on their way with Sasa Kalajdzic extending the lead before Arsenal loanee Sead Kolasinac pulled one back.
But Stuttgart would pull clear as late goals from Philipp Klement and Daniel Didavi emphasised Schalke's struggles.
Cristiano Ronaldo scored for Juventus as they were held to a 1-1 draw against Verona.
The reigning Serie A champions are seven points behind leaders Inter Milan following the stalemate as Ronaldo's effort just after the interval was cancelled out by Antonin Barak's strike.
Lazio spurned the opportunity to move into the top four as they lost 2-0 at Bologna who claimed the points courtesy of goals from Ibrahima Mbaye and Nicola Sansone.
Elsewhere, Emmanuel Gyasi hit a brace as Spezia came from two down to draw 2-2 at home with Parma.
The visitors could have moved to within two points of safety as Yann Karamoh and Hernani Junior had them on course for just a third win of the campaign before Gyasi struck.
Kylian Mbappe grabbed two more goals as Paris St Germain thrashed bottom side Dijon to move to within a point of Ligue 1 leaders Lille.
Everton loanee Moise Kean opened the scoring early on before Mbappe converted a penalty and bent home a decent effort with Danilo heading in to give Mauricio Pochettino's side a 4-0 win.
Metz moved to fifth as Vagner Goncalves hit a last-gasp winner in a 2-1 comeback victory at Bordeaux, who had taken the lead through Samuel Kalu before Thomas Delaine levelled.