Everton struck twice in injury time to earn a deserved win after Birmingham threatened to snatch a point.
Yakubu struck from close range to give Everton the lead after 10 minutes as David Moyes' side dominated.
Birmingham survived a succession of near misses and equalised through Olivier Kapo's header after 80 minutes.
But Lee Carsley drove in a 20-yard finish in the dying seconds before substitute James Vaughan showed lightning pace to add a third.
Everton flew out of the blocks and Yakubu had already gone close before hitting the target after 10 minutes.
Mikel Arteta released Steven Pienaar and he laid the ball perfectly into Yakubu's path for the Nigerian to score from six yards.
606: DEBATE
Birmingham were penned in their own half, but broke the shackles for Kapo to burst forward and force a fine diving save from Tim Howard.
Everton lost experienced defender Alan Stubbs when he limped off after 22 minutes, to be replaced by Phil Jagielka.
Yakubu's power was causing havoc, and he bustled past Johan Djourou and forced Maik Taylor into a crucial block after 25 minutes.
And he had another chance to add a second three minutes after the interval when he raced on to Arteta's free-kick but pulled his finish across the face of goal.
Everton were in danger of regretting not killing Birmingham off, and it took a timely tackle from Jagielka to deny Cameron Jerome in the area.
Yakubu had been a constant danger, and it needed a fine tackle from Djourou to block him before he unleashed a fierce 25-yard drive which Taylor was grateful to hold.
Birmingham had hung on and made Everton pay for their failure to wrap up the game with an equaliser with 10 minutes to go.
Gary McSheffrey's corner found its way through to Kapo, who powered a header past Howard.
Everton sent on Vaughan, and he almost restored the lead only for his goalbound effort to rebound to safety off Djourou.
And as the game went into injury time with Birmingham holding on for an unlikely point, Everton struck to sink Steve Bruce's side.
Carsley lashed a long-range drive past Taylor from 20 yards after Birmingham failed to clear Phil Neville's long throw.
Youngster Vaughan then showed speed and composure to latch on to Carsley's header to race clear and beat Taylor to seal the win.
Everton manager David Moyes:
"I was delighted with Lee Carsley's goal because I'd been a bit disappointed with his shooting on a couple of earlier efforts.
"I was going to tell him to stop shooting but I'm glad I didn't after seeing that one fly in. Overall I felt we deserved it - three good points and three good goals."
Birmingham manager Steve Bruce:
"We were average early on and Everton were on top, but we showed great resilience. It is not the first time this season I've come away thinking we should have had something from a game.
"We have to learn from it, but I do think we showed some of the qualities you need in this division."
Everton: Howard, Neville, Yobo, Stubbs (Jagielka 22), Lescott, Arteta, Carsley, Osman (Vaughan 80), Pienaar (Gravesen 85), Cahill, Yakubu.
Subs Not Used: Wessels, McFadden.
Goals: Yakubu 10, Carsley 90, Vaughan 90.
Birmingham: Maik Taylor, Kelly, Schmitz, Djourou, Ridgewell, De Ridder (Forssell 79), Muamba, Nafti (McSheffrey 71), Larsson (O'Connor 52), Kapo, Jerome.
Subs Not Used: Kingson, Danns.
Booked: Kelly.
Goals: Kapo 80.
Att: 35,155
Ref: Mike Riley (Yorkshire).
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