Totti wrote his name into the record books as his first-half penalty in a 3-1 victory over 10-man Genoa saw the veteran striker become the league's joint-second highest scorer of all time.
The 36-year-old needed one more goal to match iconic AC Milan striker Gunnar Nordahl's career haul of 225 goals and it arrived from the penalty spot with 15 minutes on the clock.
Genoa battled hard to spoil Totti's night, though, and Marco Borriello ensured the second half would be a contest by converting a spot-kick of his own, against his former club, just before the break.
Teenage defender Alessandro Romagnoli then took his first step towards chasing Totti's record with his maiden league goal and Simone Perrotta put the result beyond doubt after Juraj Kucka was dismissed following an angry exchange with Totti.
Earlier, Rodrigo Palacio scored twice from the bench as Inter Milan came back to seal an impressive 3-2 victory at Catania.
The Sicilians were pushing hard for a Europa League place and took a quick two-goal lead through Gonzalo Bergessio and Giovanni Marchese. A gritty Inter side steadily forced their way back into the game, however, with substitute Palacio following up Ricky Alvarez's 52nd-minute header.
Palacio then scored at the death to keep the former European champions within a point of the Champions League positions.
Substitute Marcelo Larrondo headed a late winner at the Stadio Artemio Franchi to boost Fiorentina's own top-three ambitions with a 2-1 win over Chievo.
La Viola, who went down 2-1 at Bologna on Tuesday, started on the front foot and took an early lead through Manuel Pasqual's fine free-kick.
Chievo substitute Isaac Cofie got the visitors back on level terms seven minutes before half-time but Larrondo had the last word with the decisive goal 12 minutes from time.
There was a managerial casualty as Antonio Di Natale's 150th Serie A goal decided a 1-0 win for Udinese that ultimately cost Pescara boss Cristiano Bergodi his job.
The Delfini had lost six of their last seven matches and Di Natale ensured both a seventh defeat from eight and a change of management at the Stadio Adriatico, with the club set to name Bergodi's replacement on Monday.
Sampdoria climbed into the top half of the table and above Parma as Mauro Icardi decided a 1-0 victory at the Stadio Luigi Ferraris.
The tie was settled as Argentinian striker Icardi ended his own two-game drought by converting an easy finish following a mistake from Parma goalkeeper Antonio Mirante.
Parma's neighbours Bologna, meanwhile, took a significant step towards securing their future in the top flight by ending Cagliari's seven-game unbeaten run with a 3-0 win at the Renato Dall'Ara.
Saphir Taider's early opener proved enough to earn Stefano Pioli's men back-to-back victories for the first time this season with Alessandro Diamanti making the points safe midway through the second half.
A red card for Francesco Pisano saw the Sardinians reduced to 10 men before substitute Cristian Pasquato added gloss to the scoreline as Bologna opened an 11-point gap on the bottom three.
Elsewhere, Giacomo Bonaventura scored in either half to seal a 2-0 win over Siena that moved Atalanta nine points clear of the drop zone.
Bonaventura opened the scoring with a cracking strike in the opening minutes and sealed the win midway through the second half with another fine effort.
Siena, who are five points adrift of safety, occupy the final relegation spot and lead Pescara and Palermo on goal difference alone.
The Sicilian strugglers also endured a difficult afternoon and had to settle for a single point from a goalless draw at Torino.