Starter Derek Anderson has missed practice this week with a concussion and hasn't been cleared to play. He's listed as doubtful. Max Hall went on the injured reserve list, forcing Skelton to make his first career start.
"I didn't really have a lot of [choices]," Whisenhunt said.
The team signed quarterback Richard Bartel to fill Hall's spot on the roster. Whisenhunt said he hopes Anderson, who has yet to be cleared for play by doctors, will pass the required test Saturday and be the team's third quarterback.
Arizona has lost seven in a row going into Sunday's game against the Broncos, whose coach, Josh McDaniels, was fired this week.
Skelton, a fifth-round draft pick out of Fordham, was 3-of-6 for 45 yards and was sacked once in his NFL debut in the fourth quarter of a 19-6 loss to St. Louis this past Sunday. His first pass was a 22-yard completion to Steve Breaston on third-and-16.
Whisenhunt said Skelton's "command of the offense was a lot better."
"I think that, coupled with the fact that he handled himself pretty well last week in the game, makes you feel that he's a lot better prepared now than he was earlier," Whisenhunt said. "It doesn't mean that it's going to be great quarterback play, but we're hopeful that he can get in there and handle it well and make some plays for us."
Skelton had been used almost exclusively as the quarterback of the scout team in practice, simulating the opponent for the coming week.
"It's one thing to sit back and watch the reps and learn by film study and learn by watching someone," Skelton said, "and it's something else to be in there getting the reps. It definitely benefited. A lot of plays I'm real comfortable with and a lot of plays the first time I ran them was this week."
The 6-foot-6 Skelton grew up in El Paso, Texas, but found his way to the Bronx and Fordham, where he led the Football Championship Subdivision (formerly Division I-AA) with 3,708 yards passing in 2009. His uncle Javier Loya owns a share of the Houston Texans and played quarterback at Columbia.
The Cardinals considered Skelton a long-term project. But when Anderson was ineffective and, as it turned out, had a concussion, then Hall dislocated his left shoulder, the job fell to the third-stringer.
"They'll definitely still be some nerves," Skelton said. "It will probably be tempered a little bit because I did get to play a little bit last week, but at the same time, it's still my first start. I'm not a guy that gets real nervous, but I'll probably be real anxious."
Cardinals quarterbacks have combined to throw just eight touchdown passes this season -- second worst in the NFL -- against 16 interceptions.
Linebackers Clark Haggans (groin) and Joey Porter (knee) are questionable but are expected to continue playing. Wide receiver Breaston (knee), defensive end Calais Campbell (ankle) and kicker Jay Feely (groin) are probable.
Information from ESPN.com's John Clayton and The Associated Press was used in this report.