And this time, the rest of the Bills -- on offence, defence and special teams -- showed up to support Spiller who scored twice and finished with 123 yards rushing to spark a 35-17 win over the Kansas City Chiefs in Buffalo's home opener. It was a much better effort than how Buffalo opened the season with a bumbling 48-28 loss to the New York Jets last week.
The same can't be said for the Chiefs, who followed up one dud with another a week after opening the season with a 40-24 loss to Atlanta.
Spiller picked up where he left off a week earlier, after he had career-best 169 yards rushing in taking over after Jackson sprained his right knee against the Jets.
"It's always better to answer the questions when you win," said Spiller, who giggled several times at the podium. "Fred Jackson challenged me today, when he told me to put the team on my back. So when that comes down from the leader in our room, you have to step your game up. I was ready to go today."
With Jackson expected to miss another three weeks, Spiller scored on 17- and 5-yard runs to put the Bills ahead 14-0 early in the second quarter, a lead that would balloon to 35-3 late in the third.
"C.J.'s a stud. That kid can run," centre Eric Wood said. "We've got plenty of weapons, and the good thing is we're going to get Fred back."
With 292 yards on 29 carries, Spiller is off to such a hot start that he's averaging 10.1 yards per rush. That's the highest average by an NFL player with a minimum of 25 carries through the first two games of a season since 1963, when Jim Brown averaged 11.3 yards (34 carries for 394 yards).
The Bills' defence finally showed signs of its high-priced potential after failing to make a dent last week.
Kyle Williams had two of Buffalo's five sacks. Mario Williams -- the team's high-prized off-season free agent -- recovered quarterback Matt Cassel's fumble, which set up Scott Chandler's 10-yard touchdown catch.
And linebacker Nick Barnett had a momentum-turning play late in the first half. That's when he forced Kansas City running back Peyton Hillis to fumble at the goal line to preserve Buffalo's 21-0 lead.
"We had a sense of urgency. It was just different from the very beginning," Mario Williams said. "We went out there and put it all on the line. Unfortunately, that didn't happen last week, but we have to build on this and continue."
Quarterback Ryan Fitzpatrick shrugged off last week's three-interception outing by going 10 of 19 for 178 yards and two touchdowns, including a 49-yarder to Stevie Johnson. And Buffalo's special teams contributed: Leodis McKelvin returned a punt 88 yards.
It was a complete reversal for the Bills who turned the ball over four times against the Jets, failed to get any pressure on Mark Sanchez and allowed Jeremy Kerley to return a punt 68 yards for a score.
For the Chiefs, it was the same-old sloppiness, for a team that's been outscored 75-41 and is opening a season 0-2 for the sixth time in seven years.
"I thought that we would be better, and we're not," coach Romeo Crennel said. "So we have to try and figure out what that is. From what I've seen, if we do what we're supposed to do, then we would be better."
KC's offence managed just 71 yards on its first five possessions and then coughed up the ball on its sixth, when Hillis fumbled at the goal line.
"I messed up and let the team down," Hillis said. "I put the blame on myself."
Cassel finished 23 of 42 for 301 yards with two touchdowns and an interception, with much of that production coming in the fourth quarter. Dwayne Bowe scored both touchdowns on 33- and 2-yard catches.
The Chiefs were so thoroughly outplayed on both sides of the ball in the first half that Spiller's 139 yards from scrimmage nearly matched Kansas City's 148 yards net offence.
The Bills had additional incentive to win the game in paying tribute to Marcell Dareus. The second-year defensive tackle played after travelling to his native Alabama to mourn the shooting death of his younger brother.
"He's going through a rough time, but he felt responsibilities here," Kyle Williams said. "He always picks our team up and we're glad that he's back."
Despite being bothered by a shoulder injury, Dareus had a sack, two tackles, including one for a loss.
"The team rallied up around me. This is my release from whatever is going on in the outside world," Dareus said. "I focused in on the football field and took everything else out of my head."
Notes: Spiller became the fourth Bills player to reach 100 yards in the first two games of a season, joining Jackson, Thurman Thomas and O.J. Simpson, who did that twice. ... Chiefs TE Kevin Boss will be re-evaluated after leaving the game with a head injury in the second quarter. CB Javier Arenas hurt his neck and did not return. ... McKelvin's TD return was the second of his career, and the second-longest in team history, 3 yards short of the record set by Keith Moody in 1977.