Mariano was definitively promoted to the main squad by manager Zinedine Zidane on 20 August 2016, after a back injury to striker Karim Benzema. One week later, Mariano made his senior debut during a 2–1 win over Celta de Vigo, replacing Álvaro Morata in the 77th minute. On 26 October, again from the bench, he scored his first goal for the "Merengues" to conclude a 7–1 win at Cultural y Deportiva Leonesa in the Copa del Rey. In the second leg, he added a hat-trick for a 13–2 aggregate win, including a 23rd-second goal that was his team's fastest goal in the competition. Mariano scored his first top-flight goal on 10 December, equalising in a 3–2 comeback victory at home to Deportivo de La Coruña. Later that month, he was part of the squad that won the 2016 FIFA Club World Cup in Japan, but did not appear in either of Real Madrid's matches. Mariano made eight appearances when Madrid won the 2016–17 La Liga. He was a back-up when Madrid won the 2016–17 UEFA Champions League.