Asenjo retained his starting spot throughout the 2014–15 campaign but, on 29 April 2015, in the dying minutes of a 1–0 loss to former side Atlético, he tore his ACL for a third time while attempting to make a save. After an excruciating rehabilitation process, he made his return to the squad on 23 February 2016 when he was named on the bench by Marcelino García Toral for the Europa League fixture against Italy's Napoli. The following month, and in the same competition, he played his first game in nearly 11 months and kept a clean sheet in a 0–0 draw (2–0 aggregate win) at Bayer Leverkusen.
In March 2015, Asenjo received his first ever callup to the senior national team, being named in Vicente del Bosque's squad for a UEFA Euro 2016 qualifier against Ukraine and a friendly with the Netherlands. He did not make his debut until 29 May the following year, in a 3–1 friendly win over Bosnia and Herzegovina at the AFG Arena in St. Gallen, Switzerland; he was the first footballer from Palencia to win a cap since Jesús Landáburu 36 years prior.