After Ronaldo hit his 20th career hat trick in an 11-minute span to help Madrid rout Getafe 4-0, an insatiable Messi did him one better by netting four times in Barcelona's 5-1 thrashing of 10-man Osasuna.
Messi is on pace to break his own Spanish league record of 50 goals from last season. The forward leads the league with 33 goals in 21 rounds, chased by Ronaldo on 21.
Barcelona maintained the 15-point difference with Madrid, and restored its 11-point gap over Atletico Madrid after it lost 3-0 at Athletic Bilbao.
Madrid hosts Barcelona in the first leg of their Copa del Rey semifinal on Wednesday.
"It will be a tough game," said Ronaldo, whose first goal of the day was the 300th in his professional club career. "Barcelona is a fantastic team. We will be missing several important players (Iker Casillas, Pepe, Angel Di Maria), but that is not an excuse. It will be a great night."
Also on Sunday, Malaga hung on to win 3-2 at Mallorca to reclaim fourth place from Real Betis, which lost 3-0 at Rayo Vallecano. Betis fell to fifth place while Rayo climbed into sixth.
With the "clasico" looming, there had been speculation that perhaps Messi would sit out Sunday's game at Camp Nou.
Instead, Messi stormed to his fourth career four-goal game, with only the woodwork keeping him from matching his five-goal feat from a Champions League match last season.
"We went out there and took care of business like always," Messi said. "It was important to put the game away because it isn't easy when everyone is talking so much about the 'clasico'."
Messi's first came in the 11th, when Xavi Hernandez intercepted goalkeeper Andres Fernandez's pass and found the Argentine forward, who brought the keeper to the ground with the subtlest of feints before rolling the ball home. That gave Messi yet another record, as he has now scored in 11 straight league games, improving on the old mark of 10 that he tied last season. He has also scored in his last 16 starts overall.
Midfielder Raoul Loe surprisingly leveled for Osasuna in the 24th, but the visitors' celebration was short lived.
Defender Alejandro Arribas received his second booking for blocking Adriano's strike with his arm, leaving his team with 10 men and Messi walking up to the penalty spot. Messi slotted the ball just inside the post to restore Barcelona's lead for good in the 27th.
The penalty was Messi's 200th career Spanish league goal, making him the eighth player to reach that mark and the youngest ever by four years at 25 years old.
After Messi had hit the post with a header, Pedro Rodriguez finished off a pass from Dani Alves to make it 3-1 in the 40th from another move started by Xavi.
David Villa then participated in Messi's goals in the 56th and 58th, first working a one-two combination with the four-time world player of the year for him to score from an angle. Villa then made a back pass that Adriano sent on to Messi, who tapped in his fourth goal of the night.
Earlier, Sergio Ramos scored Madrid's first goal in the 53rd minute after fellow defender Ricardo Carvalho forced goalkeeper Miguel Moya to fumble the ball by hitting his arms in an apparent foul that went unpunished.
"It was clearly a foul," Getafe coach Luis Garcia said. "It's a pity. When you are losing you have to push forward, and that's what let them get out on the break. Madrid is the best team in the world on the counterattack."
Ahead 1-0, Madrid didn't look back.
Ronaldo finished off a counterattack from its own area in the 62nd, running onto Mesut Oezil's pass and firing the ball beyond Moya.
Three minutes later, Ronaldo made it 3-0 as he charged in unmarked behind Gonzalo Higuain to head home Di Maria's floated cross at the far post. He then dispatched a penalty kick into the lower left corner in the 72nd after Alberto Lopo fouled Luka Modric in the box.
"I'm satisfied with (my hat trick), but my task is to keep it up and give my all for this club," said Ronaldo. "I want to surpass my own personal record from last season."
The Portugal forward, rarely substituted, was taken off seconds later to the applause of the Santiago Bernabeu crowd.
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