The Tigers never looked back once they had built a 17-point lead early in the second quarter following tries by Flood and wing Matt Smith.
Fly-half Flood added another 12 points from the boot, while Leicester and England lock Louis Deacon sealed Tigers' victory when he rumbled over for a 60th-minute try after wing Marcel Garvey's touchdown briefly threatened a Worcester revival.
Wing Horacio Agulla then crossed a minute from time to secure a bonus point victory and leave Worcester to reflect on their heaviest league defeat of the season.
Joe Carlisle added two penalties and a conversion for the home side, but they remain only six points and one place above bottom club Newcastle at the league season's halfway point.
Upwardly mobile Leicester, though, are now lurking just outside the title play-off zone, climbing further away from the Premiership's lower reaches that they occupied during much of September and October when they had a dozen players on World Cup duty in New Zealand.
The only concerns for Leicester came during the dying minutes when their England centre Manu Tuilagi and his red rose colleague Deacon both limped off, making them doubts ahead of next Sunday's Welford Road clash against Sale Sharks.
Deacon, captain in the absence of a rested Geordan Murphy, made his 150th Premiership appearance, while full-back Chris Pennell led a Worcester team seeking its first league victory over Tigers since 2005.
Fit-again Pennell was one of three changes from Warriors' last league outing at Exeter, with prop Matt Mullan also recovering from injury to start and Jake Abbott packing down in the back-row alongside Sam Betty and Chris Jones.
Leicester started at a breakneck pace, leaving Worcester trailing in their wake as they cruised 10-0 ahead after just six minutes.
It was all too easy for the Tigers when Flood effortlessly breached Warriors' defence, sliding through a huge midfield gap to send an unmarked Smith scampering over.
Flood converted and then kicked a penalty from just inside Worcester's half after his opposite number Carlisle infringed, leaving the Warriors requiring a rapid recovery or be faced with little chance of challenging their heavyweight opponents.
Scrum-half Shaun Perry did not help Worcester's cause, though, retaliating to a challenge from Leicester and England number nine Ben Youngs that resulted in referee J P Doyle reversing a kickable Warriors penalty and Tigers cleared the danger.
And Worcester's miserable afternoon then deteriorated further when Flood spotted another defensive hole, and this time he finished off himself, touching down for a try that he also converted.
The Warriors were at sixes and sevens, and with almost an hour of the contest still remaining they faced a potentially painful damage-limitation exercise.
Carlisle opened Worcester's account with a penalty eight minutes before the interval, yet a dismal opening period from the home side's perspective ended in predictable fashion.
Warriors number eight Jones was sin-binned for an illegal lineout challenge on Leicester flanker Ben Woods, reducing Worcester to 14 men and handing Flood an easy penalty chance that he accepted, making it 20-3 at half-time.
Despite being a player down, Worcester reduced their deficit through a second Carlisle penalty, and when Jones returned to the fray he immediately sparked a try-scoring opportunity.
Worcester, with Jones at the hub, spun possession wide and Garvey squeezed over in the corner for a try that required television match official confirmation before Doyle awarded it.
Carlisle kicked the touchline conversion, yet hopes of a full-scale Warriors recovery were soon dashed as Leicester responded ruthlessly.
Flanker Tom Croft almost scored five minutes after Garvey crossed, but then Deacon was bundled over the line from close range, putting daylight between the teams once again.
Worcester prop Oliver Tomaszczyk collected Warriors' second yellow card of the match for a dangerous tackle on Leicester flanker Julian Salvi just before Deacon departed, before Agulla's try and Flood's conversion completed Warriors' misery.
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