Nico Gordon’s unfortunate own goal following good play between Folarin Balogun and Anfernee Dijksteel put Boro in front after 23 minutes.
Despite Paddy McNair’s second-half penalty miss, Balogun extended the visitors’ lead and returned Middlesbrough to winning ways.
Blues’ misery was compounded when Kristian Pedersen was shown a second yellow card in the final minutes.
In his first start for the Blues since his January loan move from Brighton, Taylor Richards saw his shot blocked by Jonny Howson before Lukas Jutkiewicz couldn’t quite reach Onel Hernandez’s cross moments later.
After McNair blazed over, Chris Wilder’s side went ahead when neat play between Balogun and Dijksteel cut the Birmingham defence in half and Gordon was helpless in the ball hitting the back of the net.
Four minutes into the second half and Boro squandered the chance to double their advantage when Richards brought down Isaiah Jones in the penalty area.
Etheridge got down well and pushed the ball against the post to deny McNair of his first goal of the season.
Middlesbrough managed to add breathing room between themselves and Birmingham shortly after the hour mark when Balogun topped off a quality striker’s performance with a curler past Etheridge.
Matt Crooks’ dangerous run into the hosts’ area was not dealt with and the Arsenal loanee received the ball from Marcus Tavernier before unleashing a spectacular strike for his second goal in three games.
Clear-cut chances were hard to come by for Birmingham, who look safe from yet another relegation battle with a 13-point gap between them and the bottom three, with Gary Gardner hitting a strike wide of goal and Marc Roberts unable to hit the target from close range.
Birmingham’s poor evening was complete when Pedersen was sent off in the 87th minute.
Birmingham City: Etheridge, Gordon, Roberts, Mengi (Hogan 33), Graham, Richards (Chong 55), Woods, Gardner (Bacuna 76), Pedersen, Jutkiewicz, Hernandez. Unused substitutes: Colin, Bela, Sunjic, Jeacock.
Middlesbrough: Lumley, A Dijksteel, McNair, Fry, Jones (Peltier 88), Crooks, Howson, Tavernier, Taylor (Bola 67), Balogun (Watmore 81), Connolly. Unused substitutes: Bamba, Daniels, Coburn, Boyd-Munce.
Referee: Darren Bond (Lancashire).