Michael Vick threw for 187 yards and two 13 victory anticipated season opener.
The Eagles (1-0) are coming off a 2010 season in which they went 10-6 and won the NFC East before losing to Green Bay in the wild card round of the playoffs.
They have high hopes for 2011, with Vick under center to command their potent offense and a defense that features several big additions. Philadelphia signed All-Pro cornerback Nnamdi Asomugha and acquired cornerback Dominique Rodgers- Cromartie from Arizona.
St. Louis (0-1) is trying to build itself back into a contender, going 7-9 last season after posting just six wins in the previous three.
But the Rams got off on the wrong foot Sunday, as second-year quarterback Sam Bradford (hand), running back Steven Jackson (quadriceps) and wide receiver Danny Amendola (dislocated left elbow) all suffered injuries.
Steven Jackson ran for a touchdown on the Rams' first play from scrimmage, bursting through a big hole in the line and shading to the left before outracing the Eagles' secondary for a 47-yard score.
But he touched the ball just once more, and his absence for the majority of the game hampered St. Louis' offense. While the Rams totaled 335 yards, they were just 2-for-12 on third downs and didn't reach the end zone again after Jackson's run. They also incurred nine penalties for 60 yards.
"When you play good football teams, the first thing you've got to do is make sure you don't beat yourself, and we didn't do that today," said Rams head coach Steve Spagnuolo. "We suffered the consequences."
During the rest of the first half, St. Louis punted twice and got a 49-yard field goal from Josh Brown about five minutes into the second quarter.
The struggles allowed the Eagles to take control.
They responded to Jackson's score with a drive featuring several big gains. Vick completed a 41-yard pass to DeSean Jackson and, after the Rams had the Eagles pinned in a 3rd-and-11, Vick found Jason Avant for a 20-yard pickup. A roughing-the-passer penalty on the play put the ball at the 10.
Faced with another third down, the Eagles found the end zone. Vick dumped a short pass to McCoy near the line of scrimmage, and the versatile back sprinted up the middle to complete the seven-yard score with 8:13 left in the quarter.
Despite not having Steven Jackson for the majority of their next possession, the Rams reached the Eagles' 29. That was mostly thanks to running back Cadillac Williams, who signed with the Rams in the offseason.
But as Bradford went to hand the ball off to Williams, he stumbled and used his hand holding the football as support. Darryl Tapp knocked it out and Juqua Parker picked it up in the backfield, running 56 yards unimpeded to the end zone.
"After they got the first touchdown, it was important to calm down and just weather the first-quarter storm, stay in rhythm," Vick said.
The Eagles had a few chances to increase their lead, but were thwarted by a turnover and poor clock management.
Vick scrambled or passed for 51 total yards on four consecutive plays to bring the ball to the St. Louis 15 with six minutes to go. But two plays later, former Eagle Quintin Mikell rushed in on a corner blitz, hitting Vick from behind and forcing a fumble that James Laurinaitis recovered.
After forcing St. Louis to go three-and-out, Philadelphia had another chance to score. It took over at its own 35 and was deep in Rams territory with about a minute to go.
But the Eagles had no timeouts left; they burned their third after the first play of the drive.
Because of that, Vick had to spike the ball with 15 seconds left after completing a pass to Brent Celek to convert a third down and put the ball at the St. Louis 11.
Then, the Eagles couldn't get back to the line of scrimmage for a play and incurred a delay-of-game penalty. They took one shot at a touchdown, but DeSean Jackson didn't catch Vick's pass in the back of the end zone before the ball hit the ground, and Alex Henery came out for a 34-yard field goal.
After Brown missed a 47-yarder on the opening drive of the third quarter, the Eagles put together a 63-yard touchdown drive.
Vick, who signed a $100 million contract at the end of August, ended it with a six-yard pass to Jackson.
He rolled out to his left and, despite needing to take several steps back because of pressure from Rams linebacker Brady Poppinga, threw a strike to the back of the end zone.
The game only got more lopsided. Brown kicked a 23-yard field goal with 1:09 left in the third, and McCoy had a 49-yard TD run near the middle of the fourth.
Amendola and Bradford were both injured during the fourth quarter. The receiver suffered his injury on a six-yard reception less than two minutes into the frame, while Bradford left after completing a 31-yard pass to Brandon Gibson.
Henery kicked the first field goal of his career. The Eagles picked him in the fourth round of this year's draft after a standout career at Nebraska, where he hit 89.5 percent (68-of-76) of his FG attempts -- an NCAA record...Sunday's game marked the debut of Juan Castillo as the Eagles' defensive coordinator. Castillo was the team's offensive line coach for the previous 13 years...Bradford, the first overall pick of the 2010 draft, was the offensive rookie of the year last season.