The Purchasing Managers Index reached 46.2 in the region, an eight-month low.
For the second consecutive month, Ireland was the only nation in the eurozone to show an expanding manufacturing sector in September, with a PMI at 52.4, a four-month high.
Numbers above 50 indicate expansion, below 50 is contraction.
Markit said Germany's manufacturing sector reached a two-month high, but remained in contraction with a PMI of 46.8. Spain achieved a 15-month high but also remained in negative territory at 45.3.
The Netherlands hit a six-month low at 48.2. Italy had a three-month low at 45.1.
The PMI in France reached 44.5, a three-month high.
"The downturn clearly remains severe," said Markit Chief Economist Chris Williamson.
"The ongoing steep pace of manufacturing decline suggests that the region's recession will have deepened in the final quarter of the year, extending into a third successive quarter. With official data lagging the PMI, the rate of GDP decline is likely to have gathered pace markedly on the surprisingly modest 0.1 percent decline seen in the third quarter," he said.