Portuguese international Ronaldo, who set the previous best of 40 last term, nodded home an Angel di Maria centre in the 74th minute at the Bernabeu for Real Madrid's second in a 3-1 win against Sporting Gijon, his 53rd goal in all competitions this term.
Messi matched him around two hours later by netting his and Barcelona's second of the night from the penalty spot in a 2-1 victory at Levante.
The Argentine World Player of the Year earlier curled in Barca's equaliser and has 63 goals overall, four short of the all-time record of 67 set by former Bayern Munich striker Gerd Muller in the 1972/73 season.
Already Barca's leading scorer at only 24 years of age, Messi was characteristically modest in a pitchside interview after the game in Valencia, saying it was vital to keep the pressure on Real.
"Luckily things are going well [for me] but the important thing is that the team performs well so we can challenge for the title," he said.
Real, who lead Barca by four points with five games left and play at their arch rival's Nou Camp stadium in a week's time, also equalled the record for goals scored in a season of 107 set under Welsh coach John Toshack in 1990. Barca have 96.
"The team with 107 goals deserves to finish the season with the title," Emilio Butragueno, who played in Toshack's side and is now a club director, said in a television interview.
Assistant coach Aitor Karanka added at a news conference: "It's a result of the work of a fantastic group of players who give joy [to the fans] and who deserve to be champions."
