A day later, Manchester United became the first team in the competition's history to progress after a 2-0 first-leg home defeat, with Marcus Rashford's injury-time penalty sealing a 3-1 win at Paris Saint-Germain that saw them edge through on away goals.
Simeone, whose side take a 2-0 lead to Juventus for their second leg on Tuesday, sees no reason why people should be shocked by such results.
"We've seen that there are always complex and very difficult situations in cup games," he said ahead of Saturday's La Liga game with Leganes. "They're split into two, and the one who plays the best makes the difference.
"It's great. All the opponents are difficult and that's what we're seeing in the Champions League.
"It doesn't surprise me because all the teams have improved and there's a lot of competition. People who watch little football are more surprised by these results; those who watch more are less surprised."
United's win came thanks to a controversial VAR-influenced decision to penalise Presnel Kimpembe for handball, while the video assistant also caused a stir with certain incidents in Madrid's defeat and Porto's win over Roma.
Simeone, though, is not prepared to become distracted by thoughts of more debatable decisions to come.
"I understand your concern and focus on the details of Tuesday, but we're thinking about the game [against Leganes]," he said. "We have to play an important match. Then, we will think about things we can't control.
"I like Leganes. [Mauricio] Pellegrino's work is fantastic. He's done well already with other teams. Once again, he has managed to create a commitment from his players to play for the good of the team. I have great respect for coaches who can do this.
"We're not in the same comfortable situation as Juventus in their league, where there's a huge gap. We have to keep competing as we have always done, and we'll use the players we think most convenient to take the game where we want it to go."
Madrid's defeat has led to speculation that Santiago Solari will not last until the weekend, with Goal revealing that president Florentino Perez is ready to replace him as coach with Jose Mourinho.
When asked for his view, Simeone said: "It doesn't seem fair to give my opinion now as I'm not asked when things are going well. If he has something to say to me or me to him, we'll do it by phone."
Simeone did, however, appear to encourage Atletico's cross-town rivals to proceed with plans to establish a women's team.
"There are still a lot of things to improve," he added at his news conference on International Women's Day. "There's a huge future and we're very proud of our Atletico girls, and hopefully all the big clubs will have [women's] teams, too."