Such an emphatic victory comes as Barcelona's attacking threat is preparing for an additional injection of creativity with the 25-year-old Coutinho.
Messi, 30, made his debut for Barca in 2004 and has since become one of the most revered footballers of all time, leading the club to four Champions League titles.
Ernesto Valverde's side refused to let their 1-1 Copa del Rey draw at Celta Vigo on Thursday spoil their trip to the Hospital de Sant Pau in Catalonia.
He marked his 400th game in La Liga by opening the scoring in the 12th minute, when he volleyed Jordi Alba's cushioned header into the net.
Barcelona are in relentless form at the moment and the scary thing is they're only going to get better now that Coutinho has joined from Liverpool for £142 million.
Man captures video of "patient dumping" outside Baltimore hospital
The family told Baraka that the hospital had put the woman in a cab to a homeless shelter and that's where the mother found her. Suntha also said he has reached out to Baraka to thank him for the video and to thank him for bringing the situation to light.
Sony Michel, Nick Chubb a dynamic duo in wild Rose Bowl
Sandwiched between them was a 75-yard touchdown run in the second quarter, the eighth-longest touchdown run in Rose Bowl history. I never get to put this jersey on again, I never get to play with coach [Lincoln] Riley again". "It's been a wild ride".
Barcelona sign central defender Yerry Mina from Palmeiras
He helped the team win Brazil's notorious competitive Campeonato Brasileiro for the first time since 1994 in his debut season. The Colombia global will sign a 5-1/2 year contract with the Spanish side.
Ousmane Dembele and Luis Suarez both came close before the Uruguayan forward battered home the second in the 38th minute. The striker controlled the ball with his left foot before sweeping home with his right for his 11th goal of the season and his sixth in a five-round scoring streak.
However, Messi insists that he will continue with Barcelona regardless of Spain's political climate.
Barcelona reserve-team striker Jose Arnaiz debuted in the league as a late substitute.
But they weren't enough for the win amid an uninspiring performance by Cristiano Ronaldo, and poor defending by Marcelo and the rest of Madrid's backline.
The three points cancelled out second-placed Atletico Madrid's win over Getafe on Saturday to restore a nine-point advantage. He had done so during negotiations for his most recent renewal.