With seven minutes to go and with Madrid comfortably winning 2-0 after goals from Vinicius Junior and Sergio Ramos, the teenager was introduced to the action for his debut which will go down in the history books.
Romero has already been compared to Lionel Messi due to his stature and style of play, cutting in from the wing and utilising little bursts of pace during his incisive dribbles.
He was born on 18 November 2004, and is eligible to play for both Mexico and Argentina at a senior level - another reason the Messi comparisons have already started. His first coach at international level, Alejandro Sagesse, wants him to write his own story, however.
"He played a great South American championship. He has a big future,” he told AFA.
"The word is caution. We are talking about a kid of 15 years old. Does he play well? Yes, but his document says Luka Romero, not Lionel Messi.
"He has to write his own story. It is logical that they want to compare him because there are comparisons all the time, whether one agrees or not. This is an excessive comparison, he is being compared to a huge player."
The previous record held for the youngest player in La Liga history dated back to 1939 when Sanson made an appearance for Celta Vigo at the age of 15 years and 255 days old.
Even though he is eligible to play for both Mexico and Argentina, he has expressed a desire to feature for the latter, saying to the AFA in 2018:
"My whole family is Argentine; my dream is to wear the Albiceleste shirt."