Westbrook rushed for 136 yards and a touchdown in place of the injured Gore, and the 49ers sent punchless Arizona to its sixth straight loss, 27-6 on Monday night in a shower of boos from the Cardinals' home crowd.
The only fireworks Arizona mustered came during Derek Anderson's postgame tirade over questions about why he was laughing on the sideline with his team down 18 points.
Gore is done for the season with the hip injury, a team source told ESPN Insider Adam Schefter late Monday night.
Westbrook had 9 yards on five carries all season. He ran 23 times in his 21st career 100-yard game, but first since Dec. 7, 2008, for Philadelphia against the New York Giants.
"I think we have a lot of young guys, some of them have seen some of the things I've been able to do over the course of my career, some of them just don't know," he said. "They just see a guy running around the practice field. For me, it meant a lot to have an opportunity to go out there and play and have an opportunity to have success."
San Francisco (4-7), beaten at home by Tampa Bay 21-0 last week, improved to 3-1 since Troy Smith became starting quarterback and pulled within a game of co-leaders St. Louis and Seattle in the anemic NFC West.
Arizona (3-8), the two-time defending division champion, has not lost this many in a row since dropping eight straight in 2006, Dennis Green's final season as coach.
Anderson had a postgame meltdown reminiscent of Green's Monday night "they are who we thought they were" in 2006.
It came in the news conference after he repeatedly was asked by a reporter about being shown on the telecast laughing with offensive guard Deuce Lutui with his team down 18. Anderson's voice grew louder, with a few expletives thrown in, with every question.
"Every single week, I put my heart and soul into this," Anderson shouted. "I don't go there and laugh. It's not funny. Nothing's funny to me. I don't want to go out there and get embarrassed on 'Monday Night Football' in front of everybody."
The 49ers rushed for 261 yards, by far their season high and the most allowed by the Cardinals this season.
Westbrook, who led the league in rushing in 2007, was released a year ago after eight, often-spectacular seasons with Philadelphia, a move caused by a combination of his age and injury history as well as the $7.5 million he would have been due this season.
He signed with San Francisco on Aug. 16 but had hardly played until Gore went down Monday.
"I just kind of bided my time, tried to stay fresh, tried to stay focused," Westbrook said, "and when I got my opportunity, make the most of it."
The Arizona defense did not provide much resistance, as San Francisco pushed around the home team at the line of scrimmage from the start.
"We got 'outphysicaled' tonight, and that's not something I'm very happy with," Cardinals coach Ken Whisenhunt said. "I'm disappointed; I'm hurt. I feel like we have a better team than what we showed tonight, but obviously we don't. This is what we are."
Gore was hurt on San Francisco's first series, then briefly tried to come back before going out for good in the second period.
He had 25 and 15 yards in his first two carries, a sign of things to come against an Arizona defense that entered the game last in the league in points allowed.
San Francisco coach Mike Singletary said he went more with Westbrook than rookie Anthony Dixon because of experience and track record.
"He is a pro. When he came in, we told him that it is a long year, and when your number is going to be called, be ready to step up," Singletary said. "He is a bright guy, works hard and plays his role. Tonight, he had to step up and he did."
Smith didn't need to pass much, completing 11 of 23 passes for 129 yards with one touchdown and an interception.
San Francisco, a team that had not scored more than 24 points in a game all season, led 21-6 at the half. The 49ers hadn't scored that many by halftime in two years.
The Cardinals committed their 27th turnover of the season on their first play from scrimmage when Anderson and Beanie Wells botched a handoff, and Aubrayo Franklin recovered for San Francisco. On the next play, Smith threw 38 yards to Michael Crabtree for the touchdown, the receiver making a diving catch in the end zone.
Wells gained a measure of redemption on the next possession. Playing as a wideout to the right, he caught a 43-yard pass from Anderson, but a season-long red zone problem continued and Jay Feely's 31-yard field goal made it 7-3.
Ted Ginn Jr. had a kickoff return of 41 yards and a punt return for 42, both leading to San Francisco touchdowns.
The 49ers went 55 yards in 10 plays after the kickoff, Dixon leaping over from the 1-yard line to make it 14-3 with 29 seconds to go in the first.
Shane Andrus, kicking in place of injured Joe Nedney, missed a 47-yard field goal on San Francisco's first possession. He also had a 37-yarder blocked by Dominique Rodgers-Cromartie in the third quarter.
Arizona blew an opportunity late in the first half after Smith's pass bounced off the hands of Vernon Davis and was intercepted by Michael Adams at the San Francisco 42. Anderson threw three incompletions and the Cardinals punted. The boos that had started midway through the first quarter were louder than ever as the teams left the field.
The Cardinals have sold out all 50 games since moving to University of Phoenix Stadium. ... San Francisco is 5-2 against Arizona since Whisenhunt became coach in 2007, the only NFC West team with a winning record against the Cardinals in that span. ... The Cardinals were without two defensive starters -- end Calais Campbell (ankle) and cornerback Greg Toler (foot). ... San Francisco lost LB Parys Haralson (ankle) and C David Baas (jaw).
ESPN Insider Adam Schefter and The Associated Press contributed to this report.
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