Wednesday's 5-1 quarter-final first leg win set up the fascinating prospect of four meetings between the Spanish giants in 19 days after Jose Mourinho's men hammered Tottenham Hotspur 4-0 in their first leg a day earlier.
The teams do battle in La Liga on April 16, have a King's Cup final four days later, and look odds-on for a Champions League semi-final showdown on April 27 and May 3.
With both teams on course for trebles the glut of 'clasico' games, will likely decide each side's silverware count for the season.
Out of respect, Pep Guardiola and his players refused to look beyond next week's return at the Donbass Arena.
"We would be wrong if we thought that this (tie) was all over," Andres Iniesta, scorer of Barca's opening goal after two minutes at the Nou Camp, told reporters.
His Spanish international team-mate Xavi, who netted the fifth goal, added: "In football anything can happen. We could say we have a foot and a half in the semis but we have to be vigilant. They put us under a lot of pressure."
Guardiola spoke of his concerns that people were under-estimating the Ukrainians before the first leg, and once again appealed for caution ahead of the second leg.
"It is still fresh in the memory our 5-0 win over Real Betis in the King's Cup and how much we suffered in the return leg," he said referring to when the second division club scored twice in the first 10 minutes on their way to a 3-1 win in January.
The only nod Guardiola made to the forthcoming battles with Real was in relation to Saturday's league match at home to relegation-threatened Almeria, the last before the leaders visit their second-placed title rivals.
"We need to go the Bernabeu with our eight-point advantage (still in place)," he said. "Losing against Almeria is prohibited."
While Barca remained cautious, Shakhtar coach Mircea Lucescu lamented some naive defending that effectively ended their hopes of progressing.
"We have committed childish errors, and the result reflects that" the Romanian said.
"We lost the game and with a scoreline like this the tie is over. There isn't a team capable of beating Barca at present but in the future someone will."
