Brent Seabrook added a power-play goal and Dave Bolland, Kris Versteeg, Patrick Kane and Patrick Sharp also scored for the Blackhawks.
Chicago can capture the Stanley Cup for the first time since 1961 with a victory Wednesday night in Philadelphia in Game 6. A Flyers win would send the series back to Chicago for a decisive Game 7 on Friday night.
All five wins in the series have come on home ice.
Scott Hartnell, Kimmo Timonen, James van Riemsdyk and Simon Gagne scored for the Flyers. Gagne's goal with 2:36 left made it 6-4, but a half-minute later Byfuglien converted an empty-netter.
After two consecutive losses in Philadelphia, a return to the United Center invigorated the Blackhawks as did some line mixing by coach Joel Quenneville.
The Blackhawks blitzed Flyers goalie Michael Leighton with three goals in the final 7:43 of the first period and the United Center erupted as Chicago quickly found the offensive game that had helped it make the finals.
Leighton was pulled -- for the second time in the series in favor of Brian Boucher -- after giving up three goals on 13 shots.