The Welsh club entered the final two games of the season needing victories in both contests while also hoping Brighton did not win either of their own remaining matches.
With Brighton in action on Sunday at the Emirates Stadium against Arsenal, Neil Warnock’s men had the opportunity to make the Seagulls nervous if they could take three points at home against Crystal Palace.
But Wilfried Zaha, Michy Batshuayi and Andros Townsend scored for Palace, while a Martin Kelly own goal and a late Bobby Reid strike was not enough to save the Bluebirds.
It also guaranteed Brighton will remain in the Premier League next season.
The Bluebirds returned to the Premier League after five years away following a second place finish to the Championship season in 2017-18.
But the club was never able to ascend the table in the top-flight, as they spent the season battling among the relegation places.
In the January window, Cardiff also had to deal with the tragic death of former Nantes forward Emiliano Sala, who had agreed a club-record move to the Welsh club.
The 28-year-old Argentine was tragically killed in a plane crash over the English channel as he was flying from Nantes to Cardiff after saying goodbye to his team-mates at the Ligue 1 club.
Cardiff also notably endured difficult refereeing luck toward the end of the campaign, most notably in a match against Chelsea.
Cesar Azpilicueta’s equaliser was shown to be offside on replay, but the goal stood, and Ruben Loftus-Cheek’s winner consigned Cardiff to a costly 2-1 defeat.
Warnock blasted the Premier League’s referees after the match, earning him punishment from the Football Association.
Cardiff will finish out their campaign at Old Trafford against Manchester United and former manager Ole Gunnar Solskjaer, who led the Bluebirds the last time they were relegated from the top flight in 2013-14.