Christian Benteke opened the scoring, as well as his Palace account, at the Riverside Stadium with a wonderfully guided header just fifteen minutes into the game. However, more poor defending from the Eagles - and Damien Delaney in particular - allowed Daniel Ayala to head home just before half time to bring the hosts level.
Wilfried Zaha - the centre of heavy interest from Tottenham Hotspur late in the recent transfer window - restored the visitor's lead soon after the break with a well-taken finish that eventually gave the visitors a much needed victory.
Both managers forced to make changes
Aitor Karanka was able to name Victor Valdes in the starting line-up after the Spaniard missed 'Boro's win against Sunderland prior to the international break. Fellow summer signing Viktor Fischer also started while Calum Chambers was named on the bench following his loan move from Arsenal.
Meanwhile, Alan Pardew was without the injured Yohan Cabaye and Pape Souare, while Loic Remy was forced to return to parent club Chelsea for treatment on a thigh injury in midweek. This meant Joe Ledley had to come into the team along with Martin Kelly.
Benteke nets first Eagles goal
Pardew's side were the much better team in the opening exchanges and took the lead just fifteen minutes into the game through Benteke, who guided a looping header back across goal following Zaha's cross.
The Belgian's goal was the first time that struggling Palace have scored in the first half of a Premier League fixture since 2 April, but the newly formed attacking trio of Zaha, Townsend and Benteke were showing no signs of lacking quality in the final third.
Palace still have severe defensive frailties, though, and Middlesbrough found themselves level just before half time through Ayala's header.
Zaha goal enough for Palace as they earn first win of the season
It was a spirited Palace performance, much better than displays in recent months, and the South Londoners finally got what they deserved when Zaha fired home the winning goal just two minutes into the second half. A mix-up at the back caused George Friend to hesistate following a James McArthur pass and the winger beat the full-back to the ball before lacing home a left-footed shot.
Palace were forced to hang on at the end and were frustrated when the fourth official signalled an extra five minutes of additional time at the end of the 90 minutes. Steve Mandanda had to make a superb stop before Kelly cleared the rebound away from right underneath the crossbar. Jonathan Benteke replaced his tiring brother in the remaining minutes to see out the game.
The win is just Palace's third in the top-flight since 19 December while the result also gives Karanka's side their first defeat of the season following a very good start.