In a rematch of the 2014 final of Europe's biggest club competition, the same team came out on top but the roles were reversed this time as Real held the lead for the majority of the contest here on Saturday, reports Efe.
Sergio Ramos put Real Madrid ahead in the 15th minute when Toni Kroos sent a ball in from the left side on a free kick and Gareth Bale headed it onward to Atletico Madrid's goal.
Atletico's net minder Jan Oblak was beaten by Sergio Ramos, who knocked it home with his left foot to open the scoring, a goal that stood even though replays showed the Real Madrid defender was offside.
That lead then held up for the rest of the first half even though Atletico showed signs of life before the intermission, with French striker Antoine Griezmann, a new addition to the club since its last Champions final, tirelessly applying pressure on Real's defences.
Atletico then had a golden chance to tie the contest at the start of the second half when Pepe fouled Fernando Torres in the area, but Griezmann slammed his penalty try off the crossbar to the growing dread of the white-and-red-clad fans in the stands at San Siro stadium.
Time was Atletico Madrid's enemy, but Yannick Carrasco, who had come on at the start of the second half, tied up the game in the 79th minute after receiving a perfectly placed cross from Juanfran.
Two years after coming within seconds of the Champions League crown in Lisbon, now it was Real Madrid's turn to rue a late equaliser.
No more scoring would occur over the remainder of regulation or in extra time, so penalties would have to determine bragging rights in the Spanish capital.
The first seven players stepped up and deposited the ball in the back of the net - Lucas Vazquez, Marcelo, Bale and Ramos for Real Madrid and Griezmann, Gabi and Saul Niguez for Atletico, but a Juanfran attempt that hit the post put the Atletico's hopes on life support.
That left only Cristiano Ronaldo to calmly boot the game winner into the right half of the goal as Oblak dove the other way.
Real Madrid head coach Zinedine Zidane, who turned around the club's fortunes when he took over midway through the season, did not have to wait long for his first big crown.
"I dreamed of this title when I took this job. I knew it was possible, especially working with a team with this much history. We did it with effort and work and we fought to the end. The players deserve everything," Zidane, who starred for Real as a midfielder, said after the match.
Real Madrid's president, Florentino Perez, for his part, offered words of encouragement for his club's local rival, which came tantalisingly close to winning its first Champions League title two years ago before Ramos knotted the final at 1-1 with a goal three minutes into injury time in the second half.
"I feel a little sad that they've put in so much effort and haven't been able to win, but I'm convinced they'll win the Champions League," Perez said.