St. Louis fell 34-27 Sunday to the San Francisco 49ers, a loss that left the Rams 2-14.
Although they had the same league-worst record as the Colts, the Rams will have the second overall selection in the 2012 NFL draft.
The Rams also fired General Manager Billy Devaney.
"I would like to personally thank Steve and Billy for their dedication to the St. Louis Rams organization over the past several seasons," Rams owner Stan Kroenke said in a statement. "This was a difficult decision for many reasons. We have tremendous respect for Steve and Billy as people and football professionals."
St. Louis was 10-38 in three seasons with Spagnuolo as coach. The Rams went 1-15 his first year and were 7-9 in 2010 before slipping back this season, which started with six consecutive losses.