Barcelona's gap in Laliga extended the gap by 7 points, thanks to a second-half strike by Raphinha and Fermin Lopez, winning the relegation of Real Valladolid on Saturday.
Barcelona hosted Celta Vigo's second Real Madrid on Sunday, leading by 79 points. Hansi Flick's next side visited Milan in the second leg of the Champions League semifinal on Tuesday, drawing 3-3 in the mid-week.
Valladolid got a surprise six minutes later after Iván Sánchez locked on Raúl Moro's ball and shot a skewed cross into the far distance of Marc-André Ter Stegen.
The German international team returned after missing a seven-month injury, although Flick later confirmed that Wojciech Szczesny would return to the goal against Inter and Real Madrid.
"I'm really looking forward to playing this game, and when you win, it's always better," Ter Stegen told Dazn. "We keep good grades, which is important.
“Now, we’re looking forward to the next few weeks. We’re going to have some big games that are good for everyone.
"When you beat 1-0, it's hard on any team. They have nothing to lose. The fans behind them work hard tonight, but we did what needs to be done, won the game, and now we keep moving forward."
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André Ferreira's outstanding goalkeeper thwarted Barcelona's efforts to make a goal before the break, and the Portuguese rejected Ansu Fati and Ansu Fati and Lopez as tourists worked for the rhythm.
The match was briefly stopped before 19-year-old Dani Rodríguez needed medical care before being replaced by Lamine Yamal. Barcelona also lost midfielder Garvey in the second half, although that doesn't seem to be a serious problem.
"I think Garvey is OK," Flick told reporters. "I hope it's not an injury. He said he's OK after the game. But we have to wait for tomorrow.
"Dani, I'm really sad. It's tough. He comes from an injury and now he's playing the first game with us. He's really happy to have it. He shows what I've seen in training in the game. We'll take care of him and if he's back, he can always train with us."
After the interval, though, Flick's men found their grooves, and substitute Raphinha curled a pleasant half-volley to the bottom corner on the 54th minute after Ferreira par circled the Yamal cross.
Lopez completed the turnaround at the hourly mark and drove home from a distance after Gerard Martín's clinical pass.
They went to find a third, Hector Fort hit the post office after a quick counterattack, and Yamal's shot was brilliantly cleared by defender Antonio Candela.
The host threatened very late, Ter Stegen denied the substitute Juanmi Latasa, and Moro approached within a few minutes of dying, but Barcelona was determined to persevere.
"When you make nine changes, it's not easy for these people who come in," Frick said. "They're still young. I believe in them. I have the highest confidence in my players. They give everything. It's not easy to control the ball like we do when you have it."
This report uses information from Reuters and ESPN's Sam Marsden.