[3] He remained within the club's youth academy for twelve full seasons, before being transferred to Serie A giants Juventus on loan in August 2012, for €150,000 fee.

At age 20, Rugani was Empoli's star defender during their successful campaign, as he finished the season having made 40 appearances and scoring 2 goals for the club.

[9] On 18 June 2014, it was confirmed that the co-ownership agreement between the two clubs would be renewed, with the player remaining with newly promoted Empoli for the 2014–15 Serie A campaign on loan from Juventus.

[12] On 2 February 2015, Juventus bought out the remaining half of Daniele Rugani's registration rights from Empoli, for an additional €3.5 million.

[18] He made his first start with the club on 16 December, in a 4–0 win over cross-city rivals Torino in the Derby della Mole in the round of 16 of the Coppa Italia.

[24] On 7 December, Rugani scored his first ever UEFA Champions League goal on his third appearance in the competition, in a 2–0 home win over Dinamo Zagreb.

[26] Following the sale of Leonardo Bonucci to Milan in the summer of 2017, the 2017–18 season saw Rugani receive more playing time in central defence with Juventus.

[33] On 25 February 2024, Rugani netted the decisive goal for Juventus, securing a 3–2 victory at home against Frosinone, in addition to concluding his team's four-game winless run.

[37] On 9 November 2014, he was called up by Antonio Conte to the senior Italy squad ahead of a UEFA Euro 2016 qualifying match against Croatia and a friendly against Albania.

[40] Rugani made his senior international debut on 1 September 2016, with newly appointed coach Gian Piero Ventura, coming on as a substitute in a 3–1 friendly defeat to France.