Benítez left the club "by mutual consent" on 3 June 2010 with a reported £6 million pay-off; the media speculated that this was because the team had finished seventh in the Premier League, missing out on the Champions League, and suffered poor results, including the defeat by Wigan Athletic. Shortly after his departure from Anfield, Benítez made a £96,000 donation to the Hillsborough Family Support Group.
On 10 June 2010, and only a few days after leaving Liverpool, Benítez agreed a deal to become the new head coach of Serie A and reigning Champions League title-holders Inter Milan, a post that was left vacant by the departure of José Mourinho, who left to manage Real Madrid. On 15 June 2010, Benítez was presented to the Italian media for the first time after signing a two-year deal. On 21 August 2010, Benítez won his first trophy as manager, the Italian Super Cup, after they defeated Roma 3–1. On 27 August 2010 in Monaco, Inter lost to Atlético Madrid in the 2010 UEFA Super Cup. Benítez's first Serie A game in charge was on 31 August 2010 in a 0–0 draw away to Bologna in the Stadio Renato Dall'Ara. His first league win as manager came on 11 September 2010, a 2–1 win against Udinese at the San Siro.
By December 2010, Inter had slumped to sixth in Serie A, 13 points adrift of the top (although Inter played two games less), having suffered consecutive defeats against arch rivals Milan (which ended a 46 match unbeaten home record), Chievo and Lazio, as well as losing at Tottenham Hotspur in the Champions League, leading to speculation that Benítez's position was under threat. Despite criticism, Benítez guided Inter to win the FIFA Club World Cup in December 2010. Buoyed by the Club World Cup victory, he told the European champions to back him with new signings or consider whether they wanted to keep him as coach, despite the side having won the treble only a few months earlier. Benítez's demands were dismissed out of hand by the Inter ownership, with Massimo Moratti refusing to comment on Benítez's continued employment by the club. On 23 December 2010, just five days after bringing Inter to the triumph, Benítez was dismissed by Inter.