The Belgian struck after 32 minutes to become the seventh player in Inter's 113-year history to reach the 20-goal mark in two consecutive Serie A seasons, after notching 23 in his debut campaign last year.
Lautaro Martinez rattled the post for the visitors with the best chance of the second half, as Bologna were let down by poor shooting accuracy in their efforts to draw level.
Inter are on 68 points, eight ahead of second-placed rivals AC Milan, and will extend that lead to 11 points if they win their game in hand against Sassuolo on Wednesday. Bologna remain 11th with 34 points.
The result makes Antonio Conte's side huge favourites to clinch their first league title since 2010, after AC Milan and Juventus were held to draws by Sampdoria and Torino, respectively, earlier on Saturday.
"It wasn't easy playing after everyone else. But credit to the guys, after the international break it's always difficult but they kept their focus and the right spirit," Conte told Sky Italia.
Conte's side knew before kick off that they could tighten their grip on first place, and it was no surprise to see Lukaku make the decisive breakthrough.
Alessandro Bastoni whipped in a cross for the striker, whose header was superbly pushed onto the post by 21-year-old goalkeeper Federico Ravaglia, only for the ball to fall back into Lukaku's path for a simple tap-in.
"We had chances and managed to miss all of them, while they had a half chance and put it in the net," lamented Bologna coach Sinisa Mihajlovic.
Martinez was inches away from doubling Inter's lead when his shot thumped the post, and the visitors survived a late surge to see out the win.