Nine out of the 10 best-backed sides recorded victories on the day, to leave the layers reeling.
Chelsea got the ball rolling with a 6-0 thumping of Arsenal before all six favourites won in the Premier League's 1500 GMT kick-offs, along with popular Sky Bet League 1 outfit Brentford. They beat Coventry 3-1.
Manchester United's 2-0 victory over West Ham compounded a miserable day for the bookies and completed accumulators around the country, with only Leicester's 1-1 draw at Blackburn preventing further significant losses.
The Sporting Life Accumulator helped punters out - it was a 16/1 winner with Reading, Brentford, Barnet, Hamilton and Ayr all picking up three points, just as predicted.
Sky Bet's head of football Trading Paul Wiggins said: "It's been a fantastic day for punters and we're just glad Leicester were unable to add another win to their superb run.
"While the match results have been tough, the relentless run of accumulators coming in has significantly added to our losses, with one customer landing over £20k from a £25 nine-fold accumulator."
Arsenal have been dismissed from the title race by Sky Bet with their outright odds drifting to 50/1 following the 6-0 defeat at Chelsea.
The Gunners were 14/1 heading into the weekend as they sat level with Liverpool but have had their odds more than trebled to the longest price they've been all season, while the Blues are cut to 6/4 favourites after maintaining their four-point lead at the top of the table.
Such was the message sent out by Jose Mourinho's men, Manchester City's odds have actually drifted slightly, from 11/8 to 13/8, despite thumping Fulham 5-0, while Liverpool remain at 3/1 following a 6-3 win at Cardiff.
At the other end of the table, Fulham and Cardiff are 1/4 and 2/7 respectively for relegation after suffering those damaging losses.
Sunderland, Crystal Palace and West Brom were all beaten as well with that trio priced at 5/6, 5/4 and 3/1 respectively for the drop.
Norwich are out to 9/2 after they boosted their prospects by beating Sunderland 2-0 while Hull are 20/1 for the drop after seeing off the Baggies 2-0.
West Ham went down 2-0 at home to Manchester United in Saturday's evening kick-off and have seen their odds trimmed to 12/1.
TITLE RUN-IN FIXTURES
CHELSEA (Pld 31 Pts 69 GD +39)
Mar 29 - Crystal Palace A
Apr 5 - Stoke H
Apr 13 - Swansea A
Apr 20 - Sunderland H
Apr 27 - Liverpool A
May 3 - Norwich H
May 11 - Cardiff A
LIVERPOOL (Pld 30 Pts 65 GD +44)
Mar 26 - Sunderland H
Mar 30 - Tottenham H
Apr 6 - West Ham A
Apr 13 - Manchester City H
Apr 20 - Norwich A
Apr 27 - Chelsea H
May 3 - Crystal Palace A
May 11 - Newcastle H
MANCHESTER CITY (Pld 28 Pts 63 GD +49)
Mar 25 - Manchester United A
Mar 29 - Arsenal A
Apr 5 - Southampton H
Apr 13 - Liverpool A
Apr 16 - Sunderland H
Apr 21 - West Brom H
Apr 27 - Crystal Palace A
May 3 - Everton A
May 7 - Aston Villa H
May 11 - West Ham H