Born in Bergamo, Caldara began his career with hometown club Atalanta, entering in the youth categories. He played for the Primavera team from 2011 to 2014, (2013–14 season as an overage player), and on 5 May 2014, Mattia Caldara made his professional debut coming on as a second-half substitute in a Serie A match against Catania.
2014–15 season: Loan to Trapani
On 3 July 2014, he was loaned to Serie B side Trapani to gain more experience. On 14 August he made his debut as a starter in a 2–1 home defeat against Cremonese in the second round of Coppa Italia. On 7 September, Mattia Caldara made his Serie B debut as a substitute replacing Enis Nadarevic in the 62nd minute of a 2–1 home win over Vicenza. On 13 September he played his first entire match in Serie B for Trapani, a 2–1 home win against Cittadella. On 16 May, Caldara scored his first professional goal in the 96th minute of a 1–1 away draw against Avellino. On 22 May he scored his second goal in the 49th minute of a 2–1 home win over Pro Vercelli. Caldara ended his season-long loan to Trapani with 21 apparences and 2 goals.
2015–16 season: Loan to Cesena
On 10 July 2015, Caldara was signed by Serie B side Cesena on a temporary deal, with an option to purchase. On 9 August he made his debut for Cesena in a 4–0 home win over Lecce in the second round of Coppa Italia. On 20 August he played in the third round, a 4–1 away win over Catania. On 5 September, Caldara made his Serie B debut for Cesena, as a starter, in a 2–0 home win against Brescia. On 21 November, Mattia Caldara scored his first goal for Cesena in the 28th minute of a 1–1 away draw against Vicenza. On 8 December he was send off with a double yellow card in the 89th inute of a 0–0 home draw against Trapani. On 19 December he scored his second goal in the 78th minute of a 4–0 home win over Ternana. On 23 January he scored his third goal in the 57th minute of a 2–0 home win over Virtus Entella. On 7 March, Caldara was send off for the second time with a double yellow card in the 27th minute of a 2–1 home defeat against Salernitana. Caldara ended his loan to Cesena with 29 apparences, all as a starter, and 2 goals.
Return to Atalanta
After impressing on his return to Atalanta, Caldara cemented a first-team place for the 2016–17 season. On 2 October he made his debut in Serie A for Atalanta in a 1–0 home win over Napoli. On 26 October, Mattia Caldara scored his first goal for Atalanta and the only goal in the 60th minute of a 1–0 away win over Pescara. On 6 November he scored his second goal for Atalanta in the 24th minute of a 3–0 away win over Sassuolo. On 20 November he scored his third goal in 62nd minute of a 2–1 home win against Roma.
On 12 January 2017, Juventus announced that they had signed Caldara to a four-and-a-half-year contract for an initial transfer fee of €15 million, rising to a potential €25 million with add-ons. The deal also included a free loan, remaining at Atalanta until 30 June 2018.