Southampton were overpowered by their arch-rivals Portsmouth at Fratton Park and were left bottom of the Premiership after a demoralising defeat.
The visitors put up little resistance as Pompey stormed ahead from a Yakubu penalty and an Arjan De Zeeuw header.
Henri Camara rifled in an effort for Saints but LuaLua shot home after keeper Antti Niemi's error, and curled in from 20 yards as Pompey responded.
Saints rarely threatened and looked more like conceding than scoring.
The visitors had suffered a setback just minutes before kick-off when striker Peter Crouch was ruled out with a hamstring injury.
There was a highly-charged atmosphere at Fratton Park and Saints' boss Harry Redknapp emerged to a chorus of booing as he came out at his former club.
And matters quickly went from bad to worse as LuaLua was unceremoniously brought down by Niemi as he chased a chipped ball into the visitors' box.
The referee pointed to the penalty spot and Yakubu was ice-cool in nonchalantly sidefooting high into the Saints net from 12 yards.
LuaLua is felled by Niemi to earn Pompey a penalty
Pompey went close to extending their lead when Dejan Stefanovic glanced a shot over and LuaLua saw a 22-yard curler tipped over by Niemi.
But they did not have to wait long for a second as De Zeeuw headed in at the far post from a Patrik Berger cross against a rattled and subdued Saints.
Camara rifled in a shot across goal to pull one back for Saints but any hopes of a comeback were emphatically extinguished as Pompey went 4-1 up within 27 minutes.
LuaLua challenged Niemi, who made an error in coming out of his box to clear a long cross-field ball by Berger, and the home striker was allowed to shoot into an empty net.
The Saints defence was in disarray and LuaLua sent the Fratton Park faithful into raptures when he clinically curled in off the post from 22 yards after they failed to clear their lines.
Pompey could have extended their lead before the break while consolidating their lead in the second half.
Nigel Quashie had a rare chance for the visitors but his well-struck long range strike was turned round the post by keeper Jamie Ashdown.
Diomansy Kamara went close for Pompey late on before the home side clinched the win which all-but guarantees their Premiership safety.
Portsmouth: Ashdown, Griffin, Stefanovic, De Zeeuw, Taylor, Stone, O'Neil, Hughes, Berger (Cisse 57), Yakubu (Skopelitis 78), LuaLua (Kamara 28).
Subs Not Used: Fuller, Hislop.
Booked: Hughes, Griffin.
Goals: Yakubu 4 pen, De Zeeuw 17, LuaLua 22, 27.
Southampton: Niemi, Delap, Lundekvam, Jakobsson, Higginbotham, Telfer, Oakley (Bernard 45), Redknapp, Quashie, Phillips, Camara.
Subs Not Used: Anders Svensson, Davenport, Nilsson, Smith.
Booked: Lundekvam, Redknapp.
Goals: Camara 20.
Ref: S Dunn (Gloucestershire).