The headline index fell to 52.4 from 56.8 last month.
Economists were expecting a much slighter moderation to 56.5.
The production sub-component plummeted to 51.8 from 60.2, marking its lowest reading since September 2009.
The new orders sub-component also fell sharply – to 53.0 from 60.2 – the largest monthly drop since May 2011.
However, any reading above 50 on the index still indicates expansion, which means manufacturing activity in the Midwest still grew at a decent clip in March (just not as fast as in February).