Carter started in place of Clark as a precaution Monday night and made the big play that sparked the Steelers to their fifth straight win, taking the first of his two interceptions 48 yards for a touchdown in Pittsburgh's 28-10 win over the Denver Broncos.
Clark nearly died following a game in Denver two years ago because of a rare blood disorder that is aggravated by playing in high altitude, so Steelers coach Mike Tomlin decided to hold him out of the game.
He said he didn't want to risk Clark's health or burden his teammates and family members with worry.
"Ryan likes to play. He's probably hacked off at me that I didn't play him," Tomlin said. "But he will get over it."
He already is, apparently.
"My goal for this trip was to go back with the team on the plane," Clark said. "Last time I came out, I didn't make it back with them."
Clark was hospitalized in Denver in October 2007 when complications from sickle-cell trait prevented oxygen from flowing into his spleen. He later needed operations to remove his spleen and gall bladder, and he lost more than 30 pounds before he finally began feeling better more than two months later.
He missed the second half of that season, but recovered and resumed his career last season, when the Steelers won the Super Bowl.
Carter capped his night with his second interception with 15 seconds left, and Clark, dressed in charcoal sweats and a smile on the sideline, jumped up and down in celebration, then clicked the heels of his tennis shoes as he exited the field.
"I was excited for him," Clark said. "It was a big win. He did an awesome job. His first interception really put us in the game."
"I might be like Wally Pipp," he added with a chuckle. "I'd better get back fast."
Hines Ward caught two short touchdown passes from Ben Roethlisberger, including one in which he hauled in a pass in the flat and hurdled cornerback Champ Bailey on his way into the end zone, a final indignity for Denver that capped the scoring with 1:22 remaining and emptied the stadium.
Rashard Mendenhall rumbled over the Broncos for 155 yards on 22 carries as the Steelers (6-2) handed Denver its second straight loss after the Broncos opened the season 6-0 under rookie coach Josh McDaniels.
Carter's first interception return gave Pittsburgh a 7-3 halftime lead even though the Steelers had generated just three first downs and were outgained 183-54 in the first half.
An ecstatic Clark was among the first players to swarm Carter, the first defender to pick off a Kyle Orton pass all season. His only interception before throwing three Monday night was a Hail Mary that Patriots wide receiver Randy Moss pulled down in a game last month.
"I'll tell you, Ryan is like a brother to me. We've been in this thing together for a long time," Carter said. "The bond is so tight between all of us. But to know that he can't play today and knowing that he wanted to be out there, I just wanted to make sure that I went out there and played for him, and let him know I'm there for him, that we were still going to be all right."
With the Steelers clinging to a 14-10 lead in the fourth quarter, safety Troy Polamalu snared another Orton pass, this one at the Broncos 25-yard line, leading to Roethlisberger's 25-yard TD toss to rookie Mike Wallace.
Denver scored on its opening drive for the first time this season. But the Broncos had to settle for Matt Prater's 40-yard field goal after cornerback William Gay broke up a pass at the 10 to Eddie Royal, who had three receptions for 47 yards on the 56-yard drive.
The Broncos' defense retaliated for Carter's pick-six on the opening drive of the second half when Kenny Peterson swooped in and punctuated his first sack of the season by punching the ball out of Roethlisberger's hands. Rookie linebacker Robert Ayers scooped it up and rumbled 54 yards for a touchdown that gave Denver a 10-7 lead.
It didn't last long.
Roethlisberger, who was 21 for 29 for 233 yards, drove the Steelers 80 yards in four plays, hitting Ward with a 3-yard strike over the outstretched right arm of linebacker D.J. Williams to put Pittsburgh ahead for good, 14-10.
Roethlisberger drove the Steelers to the Denver 15 on the Steelers' next possession, but he threw behind Ward in the end zone and cornerback Andre' Goodman picked it off -- Big Ben's first red-zone interception since 2007.
The Steelers dominated the second half by going no-huddle with three-wide receiver sets, which kept Elvis Dumervil, the NFL co-leader with 10 1/2 sacks, on the sideline much of the time.
"We didn't stop anybody once they started going no-huddle," McDaniels said.
Clark was one of three Steelers defensive starters sitting out, joining defensive end Travis Kirschke (calf) and linebacker Lawrence Timmons (ankle). It hardly mattered as Denver managed just 59 yards on six second-half drives.
As Denver self-destructed in the second half for the second straight week, Invesco Field became a sea of yellow Terrible Towels and thousands of empty blue seats, orange giveaway pom-pons littering the aisles.
Orton was 7 for 17 for 58 yards after halftime after going 16 for 21 for 163 yards in the first half. ... 35-year-old CB Ty Law made his debut for Denver two days after signing with the Broncos.
Undrafted rookie Claudell Louis relishes the chance to play for Buffalo, an opportunity he didn't think possible on his accidental path to football.
Vince Kowalski lined up at left guard with the Packers' No. 2 offensive line earlier in the week, but was cut Wednesday.
New defensive coordinator Jim O'Neil is putting ain a 3-4 with the 49ers, and he says he will send as many rushers as it takes to harass opposing QBs.
Washington Redskins linebacker Junior Galette, recovering from last year's Achilles injury, won't return for full-time work until training camp.
Dwight Freeney, who had eight sacks with the Cardinals last season, is scheduled to visit the Atlanta Falcons next week.
Cowboys receiver Dez Bryant, whose 2015 season was scuttled by injury, is focused on returning to health and boosting the offense.