An intriguing Sunday was then concluded in deeply anti-climactic fashion as Manchester United and Manchester City played out a dismal 0-0 derby draw at Old Trafford.
Liverpool's loss meant they missed the chance to move 14 points clear of second-placed Arsenal and a step closer to a record-equalling 20th English league title.
A stunning first-half fightback from Fulham at Craven Cottage saw Arne Slot's team lose for only the second time in the league this season.
Arsenal's 1-1 draw with Everton on Saturday had given Liverpool an unexpected boost in the race for the title, but despite going ahead through Alexis Mac Allister's goal in the 14th minute, the visitors were 3-1 down at halftime.
Ryan Sessegnon, Alex Iwobi and Rodrigo Muniz all found the back of the net in a thrilling 14-minute spell, before Luis Diaz got Liverpool's second after the break.
Liverpool remain 11 points ahead of Arsenal, and need 11 more points from seven games to be assured of being crowned champions.
Later in Manchester, a wretched derby ended goalless at Old Trafford.
A troubled campaign for both the red and blue halves of the city is drawing to a close and there is now the very real danger of no Manchester representation in the Champions League next season for the first time since 1995-96.
The top four in the league qualify automatically and England are in prime position to be handed a bonus fifth place for next year's competition.
City are fifth — one point ahead of Aston Villa in sixth. Newcastle are seventh, two points behind City with two games in hand, and will move up to fifth with a win against Leicester on Monday.
United fans staged their latest protest against the club's ownership with a pre-arranged sit-in after the match, but it proved a lower-key affair than when thousands of supporters staged a march ahead of the game against Arsenal last month.
At Tottenham Hotspur Stadium, with just 10 points from 31 games, last-placed Southampton's fate was sealed with defeat by Ange Postecoglou's Spurs.
Their relegation is the joint-fourth earliest in the Premier League era - Derby's drop on March 29 in 2008 is still the earliest - but Southampton are the first team to be relegated with seven or more games to play.
"We are disappointed. It has to be a big school for everything – for us, for me, for the players, for the club – to see what we did wrong," Southampton manager Ivan Juric said.
Two first-half goals from Brennan Johnson put Southampton on course for a 25th league defeat of the season.
Mateus Fernandes pulled one back late on for the visitors before Mathys Tel struck a third for Spurs from the penalty spot in added time.
Brentford are still searching for their first home league win of the year after a goalless draw with Chelsea, whose last away league victory came four months ago.
