Carlos Alcaraz defeated Jannik Sinner in the final, 7–6(7–5), 6–1 to win the men's singles tennis title at the 2025 Italian Open. It was his seventh Masters 1000 title and 19th career title. Alcaraz also became the second-youngest man, after Rafael Nadal, to reach the quarterfinals of all nine ATP 1000 events.
Alexander Zverev was the defending champion, but lost in the quarterfinals to Lorenzo Musetti.
This tournament marked world No. 1 Sinner's first professional appearance since the 2025 Australian Open, having served a three-month suspension after reaching a case resolution agreement with the World Anti-Doping Agency. Sinner was the first Italian man to reach the final since Adriano Panatta in 1978. His loss ended a 26-match winning streak, dating to the 2024 Shanghai Masters.
Seeds.
All seeds received a bye into the second round. 
Draw.
Finals.
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Seeded players.
The following are the projected seeded players, based on live ATP rankings as of 4 May 2025. Actual seedings will be based on ATP rankings as of 5 May 2025. Rankings and points before are as of 5 May 2025.
† The player's 2025 points were replaced by a better result for purposes of his ranking as of 5 May 2025. He is defending points from an ATP Challenger Tour event (Bordeaux or Turin) instead.<br>
‡ The player's 2025 points were replaced by a better result for purposes of his ranking as of 5 May 2025. Points for his 19th best result will be deducted instead.
Withdrawn seeded players.
The following player would have been seeded, but withdrew before the tournament began.
Other entry information.
Withdrawals.
‡ – withdrew from entry list
§ – withdrew from main draw