Arsenal face Man Utd test as struggling Liverpool host Chelsea
At the bottom, Frank Lampard takes Everton to face David Moyes' West Ham, with both managers under intense pressure as the relegation trap door looms.
AFP Sport takes a look at some of the key talking points ahead of the action.
Arsenal's title charge
Arsenal v Manchester United used to be the match that defined the Premier League, pitting Arsene Wenger against Alex Ferguson in a rivalry for the ages.
In recent years the game has been reduced to a sideshow, but there is a growing sense leaders Arsenal can end a wait of nearly two decades to be crowned English champions, while United are a rising force under Erik ten Hag.
Mikel Arteta's young team are now clear favourites to claim Arsenal's first Premier League crown since the 2004 "Invincibles".
The Gunners have more points at this stage of a league season than ever before and are benefiting from the stumbles of those beneath them, particularly the inconsistency of champions Manchester City.
Aside from the game against United and a match against City in February, Arsenal's league fixtures over the next two months look kind.
Even so, Arteta believes a successful title tilt will "demand almost perfection".
Eight points behind Arsenal, Ten Hag's men travel to the Emirates Stadium without suspended midfielder Casemiro after the Brazilian was booked in the frustrating midweek draw at Crystal Palace.
Liverpool, Chelsea in clash of also-rans
After nearly two decades of sparring for silverware, the startling declines of Liverpool and Chelsea will be laid bare when they meet at Anfield on Saturday.
Just last season, Liverpool came within touching distance of an unprecedented quadruple, while Chelsea were winners of the FIFA Club World Cup.
Liverpool finished second in the Premier League and Chelsea came third, with the Reds beating the Blues in both the FA Cup and League Cup finals.
Those battles will seem like distant memories this weekend as ninth-placed Liverpool host 10th-placed Chelsea.
Both still harbour faint hopes of climbing into the top four but with injuries hurting Jurgen Klopp's side and Graham Potter's team, gatecrashing the race to qualify for the Champions League looks a tough ask.
Klopp has achieved enough in his long reign to keep the critics largely at bay, but Chelsea's Potter is on shaky ground only four months after replacing the sacked Thomas Tuchel.
Despite a huge spending spree under the club's new owners, Chelsea had lost seven of their previous 10 matches in all competitions prior to a 1-0 victory against Crystal Palace last weekend.
Potter could give a debut to Ukraine winger Mykhailo Mudryk after his £88 million ($108 million) move from Shakhtar Donetsk as he seeks to find the magic formula.
Lampard, Moyes on borrowed time
Everton manager Frank Lampard and West Ham boss David Moyes are fast running out of time heading into their crunch clash.
Either team could end Saturday at the bottom of the Premier League table depending on Southampton's result against Aston Villa, and neither will approach the game in London with much confidence.
West Ham have taken just a single point from their past seven league games and Everton have one point from a possible 18.
Rumours have swirled this week that Moyes is likely to be dismissed if he loses the game.
But the Hammers finished seventh last season, also reaching the Europa League semi-finals, and Moyes has pleaded for loyalty from fans.
"What we've given West Ham supporters in the last few years, I hope they can give us back," he said.
Former Chelsea boss Lampard, for his part, says he will not "cry" at the pressure he is under.
Fixtures (1500 GMT unless stated)
Saturday
Liverpool v Chelsea (1230), Bournemouth v Nottingham Forest, Leicester v Brighton, Southampton v Aston Villa, West Ham v Everton, Crystal Palace v Newcastle (1730)
Sunday
Leeds v Brentford, Manchester City v Wolves (both 1400), Arsenal v Manchester Untied (1630)
Monday
Fulham v Tottenham (2000)
