Manchester City have all but sealed their fourth consecutive Premier League title after a dominant 4-0 victory over Fulham, while Burnley have been relegated following their 2-1 defeat to Tottenham.
Luton are also virtually down. A 3-1 defeat at West Ham left them three points adrift of safety and with a goal difference 12 worse than Nottingham Forest with just one game remaining.
There was no twist in the title race at Craven Cottage as defender Josko Gvardiol continued his hot streak in front of goal.
The Croatian settled any City nerves by firing in on his weaker right foot after just 13 minutes.
Pep Guardiola's men were dominant but had to wait until the hour to make the points safe when Phil Foden swept in his 25th goal of the season.
Gvardiol then turned in Bernardo Silva's cross at the back post for his fifth City goal, all of which have come in his past seven games.
A 77 million-pound ($96 million) signing from RB Leipzig last summer, Gvardiol could have become the first defender in Premier League history to score a hat trick when City were awarded a penalty in stoppage time.
However, he turned down the chance to take it, allowing Julian Alvarez to round off the scoring.
Victory takes City two points clear at the top of the table and ramped up the pressure on second-placed Arsenal, ahead of their visit to Manchester United on Sunday.
Should the Gunners fail to win, City can wrap up the title when they travel to Tottenham on Tuesday.
"My players like to play with pressure, they are used to it. The players enjoy this feeling," Guardiola said.
"The destiny (of the title) is in our hands."
Spurs kept their chance of Champions League football next season alive by coming from behind to send Burnley to the Championship.
Jacob Bruun Larsen had fired the Clarets into a shock lead after Sander Berge's pass cut the Tottenham defense wide open.
Spurs had lost their last four matches, but they turned the game around to move within four points of fourth-placed Aston Villa.
Pedro Porro blasted an equalizer high past Arijanet Muric.
Micky Van de Ven then curled in the winner to at least guarantee Spurs will be in Europe next season.
"Today the Premier League is over but tomorrow we start day one of doing everything we can to get back to the Premier League," said Burnley boss Vincent Kompany.
Luton will also be back in the Championship next season after blowing a 1-0 lead and losing to West Ham in David Moyes' final home game in charge of the Hammers.
Albert Sambi Lokonga's early header gave the visitors hope of a great escape.
But second-half strikes from James Ward-Prowse, Tomas Soucek and George Earthy all but ended Luton's Premier League stay after a remarkable rise back through the leagues to get back to the top flight for the first time in 32 years.
"These players and supporters have given me the best 18 months of my life," said Luton manager Rob Edwards, who broke down in tears after full-time.
"It's a huge sorry, but a huge thank you."
With Luton set to join Burnley and Sheffield United in going down, all three promoted clubs will be relegated to expose to growing gulf between the top two divisions.
Forest missed the chance to mathematically confirm Luton's relegation by blowing a late lead to lose 3-2 to Chelsea.
Mykhailo Mudryk's opener for Chelsea was quickly canceled out by Willy Boly's header.
Callum Hudson-Odoi then seemed to have sealed Forest's survival against his former club when his fierce curling finish found the far corner 16 minutes from time.
But two goals in two minutes from Raheem Sterling and Nicolas Jackson boosted in-form Chelsea's charge towards Europe next season.
Mauricio Pochettino's men move level on points with sixth-placed Newcastle, who were held 1-1 at home by Brighton.
Crystal Palace's stunning form since the arrival of Oliver Glasner as manager continued with a 3-1 win at Wolves.
Michael Olise, Jean-Philippe Mateta and Eberechi Eze were on target for the Eagles, who climb up to 12th.
Abdoulaye Doucoure scored the only goal as Everton beat Sheffield United 1-0.
Yoane Wissa scored a 95th-minute winner for Brentford to snatch a 2-1 victory at Bournemouth.
