Kidderminster Harriers slumped to their heaviest league defeat since Steve Burr took charge on a night when both sides ended with 10 men at Highbury Stadium.
Fleetwood's Jamie Vardy and Harriers' Steve Guinan were sent off just before the half-hour with the score still 0-0.
Gareth Seddon and Magno Vieira struck for Fleetwood either side of the break.
Andy Mangan made it 3-0 and Vieira hit a second and, although Lee Vaughan's penalty pulled one back, Richard Brodie scored before Jamille Matt's reply.
The result was Harriers' worst in the Conference since a 5-2 defeat at Torquay almost four years ago to the night.
Following a quiet start, the game sparked into life on the half-hour mark when Vardy was dismissed for a dangerous tackle on Vaughan and, in the aftermath, Guinan was given his marching orders for throwing a punch.
The hosts took the lead in first-half a minute before half-time when Seddon scored from 18 yards and then Vieira bagged his brace, from the edge of the box and close range, either side of a cool Mangan finish as Fleetwood raced into a 4-0 lead inside 67 minutes.
Vaughan fired home from the spot when Shaun Beeley fouled Matt in the area two minutes later, before Brodie added a fifth - but Harriers did at least have the last word, when Matt netted a late consolation for the visitors from 12 yards.
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Kidderminster Harriers manager Steve Burr told BBC Hereford and Worcester:
"It all went wrong when we went down to 10 men and they went down to 10 men, they worked a lot harder than us.
"We were in control in the first half, then the incident where the two lads were sent off, and they were better than us in the second half.
"Maybe it's time to shake things up, and maybe freshen it up a bit."