Also, former King Manny Legace made 27 saves for the Red Wings.
After falling behind by three goals after two periods, the Kings made a furious attempt to tie the game in the third, but fell short.
They remained eight points behind Edmonton for the final Western Conference playoff berth.
Kings General Manager Dave Taylor, who locked up defenseman Aaron Miller before the game by agreeing to terms on a new four-year contract, could decide to call it a season and begin unloading veterans like Bryan Smolinski and defenseman Mathieu Schneider.
Kris Draper gave Detroit a lead in the first period and defenseman Nicklas Lidstrom tallied early in the second to make it 2-0, but Zetterberg provided the telling blow, scoring midway through the period to help the Red Wings improve to 12-1
Legace, who played 17 games for the Kings in 1998-99, withstood a wild third-period attack, stopping 14 shots to improve to 12-4-3.
Schneider and Ziggy Palffy scored for Los Angeles, which has lost four of its last six and completed a 2-3-0 homestand.