Dutch centre forward Thijs Dallinga netted twice after Riccardo Orsolini opened the scoring for Bologna, who are attempting to reach the final for the first time since winning their second Coppa Italia in 1974.
AC Milan and Inter Milan meet in a derby in the other semi on Wednesday, with the return legs scheduled for April 23 and 24.
Bologna went ahead in the 23rd minute on Tuesday when Orsolini redirected in a cross from Jens Odgaard. Italy coach Luciano Spalletti was in the stands and will have been impressed by Orsolini, who also scored in Bologna's last two Serie A matches.
Six minutes later, Dallinga slipped between two defenders to double the advantage with the outside of his rigtht foot after taking a pass from Dan Ndoye.
Ndoye again provided the assist when Dallinga finished off a counterattack after the break.
"There were clearly some errors on the goals, which you cannot afford against Bologna who along with Roma are the form team in Italy at the moment," said Bologna coach Roberto D'Aversa.
"The regrets are also that we had the chances to score and did not take them. Bologna were superior on the pitch, all credit to them."
Bologna extended their winning streak to six matches across all competitions.
The Italian Cup winners are given a Europa League spot, although Bologna are fourth in Serie A and on course to qualify for the Champions League for a second straight season.
Empoli, who are third from the bottom in the league and in danger of relegation, eliminated Juventus in a penalty shootout in the quarter-finals to reach the last four for the first time.
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