Orlovsky also played in the NFL for the Houston Texans, Indianapolis Colts, Tampa Bay Buccaneers, and Los Angeles Rams.

[citation needed][4] Despite offers from Purdue and Michigan State, Orlovsky committed to play at Connecticut, where he wanted the challenge of elevating the Huskies into a Big East contender.

[citation needed] Orlovsky became the starter at Connecticut during his freshman year when Keron Henry suffered a sprained knee.

[7] On October 11, UConn traveled to Raleigh, North Carolina to take on Heisman trophy candidate and future first round draft pick, Philip Rivers and the N.C. State Wolfpack.

Orlovsky, along with head coach Randy Edsall, served as the "face" of the UConn football program during the early 2000s.

He played in two regular season contests in 2005, including the nationally televised Thanksgiving Day game against the Atlanta Falcons.

Prior to the 2006 season the Lions traded Joey Harrington and released Jeff Garcia, while signing Jon Kitna and Josh McCown.

Orlovsky made his first career NFL start on October 12, 2008, in a 12–10 Lions loss against the Minnesota Vikings.

However, early in the first quarter when he lined up in shotgun formation, he inadvertently ran out of the back of his own end zone for a safety, in what turned out to be the margin of victory.

Orlovsky announced his intention to explore the free agent market at the end of the 2008 season rather than accept a contract as a backup quarterback in Detroit.

After the 2009 season, Grossman signed a one-year contract with the Washington Redskins, making Orlovsky the backup quarterback for the Texans.

The next week, Orlovsky went on to complete 30 of 37 passes, with 353 yards, 2 touchdowns, and 1 interception, for a total passer rating of 113.1 in his first start as a Colt against the New England Patriots, in a 31–24 loss.

On December 22, 2011, Orlovsky led the Colts on a 12-play, 78-yard drive in a comeback victory over the 10–4 Houston Texans with less than two minutes remaining in the game.

[27] On May 18, 2022, Orlovsky joined the #2 ESPN NFL crew with Steve Levy and Louis Riddick Jr., replacing Brian Griese.