3SC and Enugu Rangers suffered exits from this year's Federation Cup after losing their round of 16 matches on Wednesday.
Just inside the hour mark, 3SC's only realistic route to silverware this season looked all but over when Enyimba raced into a three-goal lead in Abuja.
The impressive Kingsley Bobby Sokari and Andrew Abalogu scored in the opening half for the Aba club and winger Chimezie Amanfor put the icing on the cake for Enyimba playing without two of their experienced strikers, Sibi Gwar and Ukeyima Akombo, who were on the bench.
3SC could only muster a consolation goal after Gbolahan Salami benefited from Bala Mohammed's failure to clear his lines.
Rangers, however, fell to Akwa United 1 – 2 at the Dan Anyiam Stadium in Owerri.
Stephen Adah put Akwa United in front before Senegalese defender, Pierre Coly put Rangers on level terms just before the break.
But it was another Senegalese defender, Ousmane Pape Sane, who scored an own goal in the 80th minute to end Rangers' Cup quest.
The Flying Antelopes are now left with the league as their only path to end a 29-year-old wait for a first domestic trophy.
A first half goal from Musa Najare was enough for Glo Premier League side, Warri Wolves to beat National League outfit, Niger Tornadoes in Akure.
At the Confluence Stadium in Lokoja, Nasarawa United held on to a first half goal from Nasarawa United to see off Sunshine Stars just as Kano Pillars edged Gombe United via Bello Kofarmata's strike in Jos.
In the clash of second tier teams in Calabar, goals from Utibe Bassey and Jonah Ambrose helped Akwa Starlets progress at the expense of Abia Warriors.
Cup holders, Heartland had to endure the lottery of penalties to progress after regulation time ended 1 – 1 with Sharks in Benin.
Bright Ejike set the tone for Heartland in the 34th minute but the lead lasted just 10 minutes as Tayo Fabiyi rallied the Blue Angels back into the contest. But Heartland won 5 – 4 on penalties.
In Minna, ABS and Lobi Stars fired blanks after 90 minutes but it was the latter that triumphed 5 – 4 through spot kicks.
FEDERATION ROUND OF 16 RESULTS
Enyimba 3 – 1 3SC
Akwa United 2 – 1 Enugu Rangers
Niger Tornadoes 0 – 1 Warri Wolves
Nasarawa United 1 – 0 Sunshine Stars
Kano Pillars 1 – 0 Gombe United
Akwa Starlets 2 – 0 Abia Warriors
ABS 0 – 0 Lobi Stars
(Lobi won 5 – 4 on penalties)
Heartland 1 – 1 Sharks
(Heartland won 5 – 4 on penalties)