Valletta became the first team to book their place in this season's Championship Pool after brushing aside the challenge of Hamrun Spartans 4-1 in a nervy encounter on Saturday.
Marsaxlokk, Floriana and Sliema Wanderers also edged closer to a top-six berth with vital victories but the hopes of Hibs and Hamrun were dealt a blow after their latest upsets.
The rivalry between Valletta, the current Premier League leaders, and Hamrun Spartans had set up the prospect of a nailbiting contest.
However, the match turned out to be a one-sided affair with the Citizens opening a two-goal lead inside the opening 17 minutes with goals from David Camilleri and Sebastian Monesterolo.
The Argentine added two more goals midway through the second half to seal a comfortable win for the Citizens who now have an unassailable 10-point lead over seventh-placed Hibs with only three matches left to play.
Hamrun's consolation goal came eight minutes from time when Valletta defender Kenneth Scicluna headed into his own net. Unfortunately, the match was marred by some ugly scenes in the Spartans' end with several seats thrown on to the pitch and scattered skirmishes between fans in the second half.
Marsaxlokk made it three wins in a row after thrashing Hibernians 5-0. The champions were in complete control after Kevin Sammut and Julio Alcorse gave them a 2-0 half-time lead.
The southerners piled on the agony for the below-par Hibs with further strikes from Mark Barbara, Jamie Pace and a Malcolm Licari penalty.
The result put Marsaxlokk well within sight of a Championship Pool berth but the same cannot be said of Hibs who must pick maximum spoils from their remaining three matches, starting with Sunday's game against Pietà, to avoid finishing in the Relegation Pool.
Old Firm rivals Sliema and Floriana, who are sharing third spot on 27 points, recorded emphatic victories in Sunday's matches at the Tedesco Stadium.
The Wanderers exerted little energy to dispose of bottom-placed Mqabba 4-0. Goals from Ivan Woods, Etienne Barbara, Noel Turner and a Mauro Bonnici own goal gave the Blues the perfect tonic ahead of Saturday's big clash against Valletta.
Floriana found it harder than expected to overcome the challenge of a solid Pietà Hotspurs side.
After a frustrating first half, the Greens finally broke their opponents' resistance with a three-goal burst from Christian Cassar, Ryan Darmanin and Yala Bolasie.
Edward Herrera pulled a goal back for the Hotspurs who are now mathematically certain of playing in the Relegation Pool.
Premier League statistics
Birkirkara: Hartvig 4; Mifsud Triganza 3, M. Galea 3, Bajada 3; Tabone 2 (1 pen.); Tamboulas, Yanchev, T. Paris, Fenech, Anastasi, Sylla.
Floriana: Darmanin 7; Micallef 4; C. Caruana 3, Mifsud 3 (moved to Hibs), Krsteski 3 (1 pen.); Brincat 2, Cilia 2, Cassar 2, Bolasie 2; M. Caruana, Sevasta. Red cards: M. Brincat (vs Mqabba); Krsteski (vs Sliema); Gauci (vs Hibs); Cassar (vs Mqabba); Bugeja (vs Marsaxlokk). Missed penalty: Mifsud (vs Msida).
Hamrun: Spiteri 7; Sultana 6 (2 pens); Effiong 5; Ryan Fenech 2, Mangion 2; Briffa, Roderick Fenech, Cucciardi. Own goals: Conceicao (vs Marsaxlokk); Scicluna (vs Valletta). Red cards: Ryan Fenech (vs Pietà); Timotic (vs Birkirkara); Briffa (vs Pietà).
Hibernians: Scerri 6; Cohen 4 (1 pen.); Alcorse 2 (moved to Marsaxlokk); Doffo, Agius, Edafe, Chukunyere, Failla, Mifsud. Own goal: Said (vs Sliema). Red cards: Failla (vs Floriana), Edafe (vs Floriana), Edafe (vs Marsaxlokk).
Marsaxlokk: Licari 7 (1 pen.); Barbara 6; Frendo 4; Sammut 3 (1 pen.); Gomes 2, Alcorse 2, Pace 2; Pullicino, Da Silva, Camenzuli, Templeman. Own goals: Borg (vs Msida); Agius (vs Floriana). Missed penalty: Gomes (vs Sliema). Red card: Conceicao (vs Pietà).
Mqabba: Pereira 6 (1 pen); Zarb 2, Silva 2 (2 pens); Gatt Baldacchino, Calleja, Nogueira. Red cards: Pereira (vs Birkirkara); Psaila (vs Birkirkara).
Msida SJ: Doding 6 (2 pens); Pedrinho 5; A. Farrugia 2, Borg 2; Baldacchino, Ogbonna, Magri, T. Farrugia. Red cards: A. Farrugia (vs Birkirkara); Brincat (vs Hibs); Pedrinho (vs Mqabba); Spiteri (vs Marsaxlokk); Doding, Cachia, Grima (all vs Sliema); Bartolo (vs Valletta). Missed penalties: Doding (vs Hibs); Pedrinho (vs Marsaxlokk).
Pietà Hotspurs: Herrera 5; Deanov 3; Kondev 2 pens, Deliminkov 2; Galabov, Goodlip, Q. Refalo. Red cards: Aquilina (vs Valletta); Kondev (vs Marsaxlokk); Montfort (vs Msida); Q. Refalo (vs Hamrun). Missed penalties: Kondev (vs Msida), Herrera (vs Hibs).
Sliema: Barbara 6 (1 pen.); Madzar 4, Woods 4 (1 pen.); Said 3; Briffa 2; Milovanovic, Muscat, Bajada, Anonam, Bartolo, Da Silva, Turner. Own goal: Bonnici (vs Mqabba). Red cards: Bajada (vs Hamrun); Pace (vs Birkirkara). Missed penalties: Woods (vs Birkirkara); Barbara (vs Floriana).
Valletta: Monesterolo 13 (2 pens); Zammit 8; Temile 3; Scicluna 2, Agius 2, Backhaus 2; Giglio pen., Mattocks, Bondin, Mifsud, Camilleri. Red cards: Zammit (vs Pietà); Mattocks (vs Mqabba); Monesterolo (vs Floriana); Bezzina (vs Hibs). Missed penalties: Monesterolo 2 (vs Pietà).
Next fixtures
Saturday (National Stadium)
Msida SJ vs Birkirkara 2 p.m.
Sliema W. vs Valletta 4 p.m.
Sunday (Hibs Ground)
Mqabba vs Marsaxlokk 1 p.m.
Hibs vs Pietà H. 3 p.m.