On 22 April, with five games to spare, Inter were mathematically confirmed as Serie A champions for the twentieth time in their history after defeating second-placed and city rivals AC Milan in the Derby della Madonnina, earning the second star above their badge.

[3] On 3 July, Croatian playmaker Marcelo Brozović joined Saudi club Al Nassr for a reported fee of €18 million, leaving Inter after eight and a half seasons.

[9] On 12 July, Inter triggered the €7 million release clause to sign promising German centre-back Yann Aurel Bisseck from Danish club AGF, who agreed to a five-year deal.

[11] On 19 July, Colombian right-midfielder Juan Cuadrado joined Inter as a free agent in a rather controversial move, after his contract with bitter rivals Juventus expired.

[12] On 20 July, after weeks of speculations, goalkeeper André Onana joined Manchester United for a reported fee of €52.5 million, agreeing to a five-year contract with the English side and leaving Inter after only one season.

[14] On 7 August, Inter signed Swiss goalkeeper Yann Sommer from Bayern Munich for a reported €6.75 million fee, penning a three-year contract with the club.

[17] On the same day, Inter filled the now-vacant left wing-back spot by signing Carlos Augusto from Monza on a season-long loan with a conditional obligation to buy for a reported total fee of €12 million plus bonuses.

[18] On 16 August, Austrian striker Marko Arnautović made his return to Inter after 13 years, joining from Bologna on a season-long loan with a conditional obligation to buy for a reported fee of €8 million.

[28] On 20 September, Inter struggled away from home against Real Sociedad in their seasonal Champions League debut, with the Spanish side taking the lead early in the game thanks to Brais Méndez, and Lautaro scoring a late equaliser to earn the Nerazzurri a 1–1 draw.

[38] On 8 November, Inter managed to beat Salzburg away from home 1–0 courtesy of a late penalty kick scored by Lautaro, and advanced to the round of 16 of the Champions League with two games to spare.

[40] On 26 November, Inter secured a 1–1 away draw in the Derby d'Italia against Juventus to maintain the top spot of the league, with Lautaro scoring the equaliser after a Dušan Vlahović goal.

[41] Three days later, the away match against Benfica in the Champions League ended 3–3, with the heavily rotated Nerazzurri side coming back in the second half with the goals from Arnautović, Frattesi, and Sánchez, after João Mário scored a first-half hat-trick against his former club.

[42] On 3 December, Inter started the new month by defeating reigning Serie A champions Napoli 3–0 at the Stadio Diego Armando Maradona, with goals from Hakan Çalhanoğlu, Nicolò Barella and Marcus Thurman.

[53] On 5 January, following Juan Cuadrado's Achilles tendon surgery,[54] Inter signed Canadian wing-back Tajon Buchanan from Club Brugge as his replacement for a fee of €8.5 million plus bonuses.

[61] On 28 January, a header from Lautaro secured Inter a 1–0 victory over Fiorentina in the last match of the month,[62] and allowed the team to regain the top spot of the league, after Juventus drew against Empoli.

[63] On 4 February, the second Derby d'Italia of the season was decided by an own goal from Federico Gatti, granting Inter a 1–0 victory at San Siro and increasing the point gap between the two teams.

[69] On 4 March, Kristjan Asllani's first goal with the Nerazzurri shirt and a penalty kick scored by Alexis Sánchez granted Inter a narrow 2–1 win against Genoa, widening the gap between Inzaghi's side and Juventus by 15 points.

Inter initially took the lead with a Federico Dimarco goal, but the Colchoneros came back with strikes from Antoine Griezmann and Memphis Depay, setting the aggregate score to 2–2, before eliminating the Nerazzurri in the penalty shoot-out.

[77] On 22 April, Inter beat Milan 2–1 in the second Derby della Madonnina of the season thanks to the goals from Acerbi and Thuram, mathematically securing their historic 20th scudetto and second star with five games to spare.

[79] Inter started May by suffering their second league loss of the season, losing 0–1 against relegation-battling Sassuolo, with the Neroverdi defeating the newly crowned champions again after doing so in the first half of the campaign and ending their 28-game unbeaten run in Serie A.