- Federico Dimarco (51')
The victory at Stadio Carlo Castellani left Inter on 15 points after five games, three ahead of second-placed rivals AC Milan, who beat Hellas Verona on Saturday. Empoli remain rooted to the bottom of the table with no points and no goals.
Inter dominated a goalless first half before scoring the opener in the 51st minute when a clearance from a corner fell to Dimarco, whose spectacular volley arrowed into the top corner.
Empoli pushed hard in the final minutes, with Inter down to 10 men after Marko Arnautovic limped off injured, but the league leaders held on to win and maintain their 100% league record.
"Few managers have won the first five games? Personal glories don't interest me," manager Simone Inzaghi told Sky Sport after the final whistle.
"We should have closed the game earlier, because then we went down to 10 men and in the last few minutes we suffered a little. With everything we created we had to make it 2-0."
The visitors started strongly creating plenty of chances, with Empoli defender Ardian Ismajli heading Matteo Darmian's header back out off the line in the ninth minute.
Inter finally broke the deadlock after Dimarco forced a corner. Empoli keeper Etrit Berisha did well to push away his effort, but when Filippo Ranocchia's headed clearance from the corner found Dimarco, there was no stopping his stunning strike.
Empoli offered some resistance after going behind and Filippo Ranocchia's free-kick forced a sharp save from keeper Yann Sommer.
Inter came closest to adding a second when Thuram chested down an Arnautovic cross before letting fly but his shot sailed just over the crossbar.
Empoli's new manager, Aurelio Andreazzoli, who replaced Paolo Zanetti on Tuesday, was unable to improve on the club's disastrous start to the season.
They are now the first team in Serie A history to have zero points and zero goals scored after the opening five games, but they at least showed some improvement from their 7-0 thumping by AS Roma last weekend.
- Matteo Marcenaro