The 19-year-old — who burst into the limelight during Italy’s opening Euro 2020 qualifiers — came on as a substitute in Turin and three minutes later scored his third league goal of the season after his double against Udinese earlier this month.
It got Massimiliano Allegri’s side back to winning ways after falling to their first league defeat of the season to Genoa before the international break.
Second-placed Napoli travel to Roma on Sunday looking to close the gap to 15 points with nine games remaining.
Ronaldo had been rested by Juventus against Genoa and the Portuguese star is now recovering from a right thigh injury picked up on international duty.
Argentina striker Paulo Dybala also pulled up with a thigh problem during the warm-up before Saturday’s game.
Kean’s form, with goals for Italy against Finland and Liechtenstein, gives Allegri more options ahead of his side’s Champions League quarter-final against Ajax.
But Juventus are without wingers Douglas Costa and Juan Cuadrado, with centre-back Andrea Barzagli also out injured.
The seven-time defending champions struggled to break down the Tuscans who were targeting a second straight win under new coach Aurelio Andreazzoli.
Empoli dug deep, allowing the hosts few opportunities, with Polish goalkeeper Bartlomiej Dragowski denying Mandzukic to the frustration of the home crowd.
Kean replaced Blaise Matuidi in the 68th minute and had an immediate impact, latching onto Mandzukic’s knock-down.
Ten minutes later, the teenager was denied a second, with a desperate one-handed save by Dragowski giving Empoli hope.
The Tuscany side remain one point above the relegation zone.
Earlier on Saturday, Igor Tudor got off to a winning start on his return as Udinese coach with a 2-0 victory over Genoa.
Former Croatian international Tudor took over a year after coming in and saving the north-eastern outfit from relegation with two wins in the last four games of the 2017-2018 season.
Stefano Okaka opening the scoring after just four minutes in Udine, finishing from a Seko Fofana cross.
Rolando Mandragora sealed a valuable three points with a volley just after the hour mark as Udinese gained some breathing space by moving four points above the relegation zone with just their third win of 2019.
AC Milan, meanwhile, travel to Sampdoria later Saturday targeting third place ahead of arch rivals Inter, who moved ahead after winning their derby clash before the international break.
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