Head coach Ken Wisenhunt confirmed on Friday that Skelton had won the battle with Kevin Kolb to start under centre for the home game against the Seattle Seahawks on September 9.
A fifth-round pick back in the 2010 draft, Skelton had a 5-2 record in his seven starts for the franchise last season, throwing for 11 touchdowns with 14 interceptions.
"It's kind of a weight off my shoulders in a sense because finally the speculating and the waiting are over," he told the team's official website.
"At the same time, there is another weight placed on them."
Kolb began last season as the starter for the Cardinals but was hampered by injuries, firstly suffering a toe problem before having to cut short his campaign due to a concussion.
He arrived in Arizona from the Philadelphia Eagles via a trade that sent cornerback Dominique Rodgers-Cromartie and a second-round draft pick the other way.
Despite his struggles so far in the desert, Kolb was handed a five-year contract extension during the off-season.