Titleholders Juventus were sent crashing to a 3-2 defeat at Sampdoria on Sunday and hapless Benevento were denied their first point of the season when they lost 2-1 to Sassuolo in stoppage time.
Federico Peluso's 94th-minute winner for Sassuolo, which came minutes after his team missed a penalty, meant that bottom team Benevento were condemned to a record-extending 13th straight defeat.
Second-placed Juve trailed 3-0 at Sampdoria before stoppage-time goals by Gonzalo Higuain, from a penalty, and Paulo Dybala made the score more respectable.
Juventus rested goalkeeper Gianluigi Buffon and defender Andrea Barzagli, who both confirmed their international retirements after playing in Monday's 0-0 draw with Sweden which meant that Italy failed to qualify for the World Cup.
The visitors missed a host of first-half chances then collapsed after the break as Sampdoria maintained their perfect home record.
Duvan Zapata headed Sampdoria ahead in the 52nd minute, Lucas Torreira blasted the second and Gian Marco Ferrari turned in Fabio Quagliarella's cross from the byline for the third.
Juve dropped four points behind leaders Napoli who beat AC Milan 2-1 on Saturday.
Benevento gifted Sassuolo the lead as a backpass was intercepted by Simone Missiroli who then left Alessandro Matri to tap into an empty net after 57 minutes.
In a game that summed up Benevento's season, Samuel Armenteros equalised eight minutes later but they almost immediately had Gaetano Letizia sent off for a second booking.
Benevento held out until stoppage time when Sassuolo were awarded a penalty for handball which Domenico Berardi smashed against the bar.
The home team's relief was short-lived, however, as Peluso headed in from a corner for the winner from the next attack.
In other matches, Luca Rigoni's early goal gave Genoa a 1-0 win at Crotone and a winning start to Davide Ballardini's third stint as their coach after he replaced Ivan Juric.
Torino and Chievo drew 1-1 as did SPAL and Fiorentina while Cagliari won 1-0 at troubled Udinese.