He played college football for the Eastern Illinois Panthers, where he made an Ohio Valley Conference championship appearance in 2001 and won the Walter Payton Award the following year.

Romo retired after the 2016 season after a preseason back injury caused him to lose his starting position to rookie backup Dak Prescott.

[28] One of Romo's early career highlights was in 2004, when (as the third-string quarterback) he rushed for the winning touchdown with six seconds left in a preseason game against the Oakland Raiders.

On fourth down with less than half a minute and no timeouts left, Romo threw the ball into the end zone, but it was intercepted by Giants cornerback R. W. McQuarters, ensuring that the Cowboys were eliminated from the playoffs with a 21–17 loss to the eventual Super Bowl XLII champions.

[62] That same month, Romo signed a five-year, $10 million endorsement deal with apparel marketer Starter,[63] but was not allowed to wear footwear on the field as the company did not have a contract with the NFL.

Romo and the Cowboys won their third straight game against the Green Bay Packers before losing to the Washington Redskins in Week 4, falling to 3–1.

[67] In what became a de facto third playoff game for Romo shortly prior to its start, the Cowboys failed to compete against the Eagles in a 44–6 road loss during the regular-season finale.

[69] During the season-opening 34–21 road victory over the Tampa Bay Buccaneers in their season opener, Romo completed 16-of-27 passes for a then-career-high 353 yards and three touchdowns.

[81] However, the following week in the Divisional Round against the #2-seed Minnesota Vikings, Romo threw for 198 yards and an interception while also fumbling thrice (losing two of them) and being sacked six times during the 34–3 blowout road loss.

[84] During a Week 7 41–35 loss to the New York Giants, Romo threw for 39 yards and a touchdown before suffering a broken left clavicle in the second quarter when he was being driven to the turf by linebacker Michael Boley.

[87] Romo's 102.5 quarterback rating in 2011 was fourth best in the league behind Aaron Rodgers, Drew Brees, and Tom Brady, and second highest in Cowboys history.

[89] During Week 2 against the San Francisco 49ers, Romo suffered a broken rib and a punctured lung on a hit from Carlos Rogers in the second quarter that forced him to miss part of the game.

[92] During a Week 16 20–7 loss to the Philadelphia Eagles, Romo left the game after attempting just two passes with no completions after suffering a severely bruised hand when he smashed it against an opposing player's helmet.

After Dallas took over with 3:33 left down 21–18, Romo threw an interception to Redskins linebacker Rob Jackson, and Washington clinched the victory with another touchdown.

"[111] Dan Graziano of ESPNDallas.com wrote that Romo's "record starts to become very hard to defend" due to "the oft-cited fact that he's got just the one playoff win in his entire career.

[119] During a narrow Week 16 24–23 victory over the Washington Redskins, with the Cowboys trailing in the fourth quarter and needing a win to keep its playoff hopes alive, Romo led the team to a touchdown drive with 1:08 remaining, with what was later diagnosed as a season-ending herniated disk injury.

[122] Garrett announced Kyle Orton as the starting quarterback for the regular-season finale against the Philadelphia Eagles, which the Cowboys narrowly lost 24–22, to miss the playoffs for a fourth consecutive year.

[136] During the Wild Card Round of the playoffs, Romo led the Cowboys to a 24–20 comeback victory over the Detroit Lions after being down 17–7 at halftime.

The officials initially ruled Bryant down at the one-yard line, but the call was overturned as an incomplete pass following a challenge from Packers head coach Mike McCarthy.

Romo started the 2015 season strong, throwing a game-winning pass to Jason Witten with seven seconds left in the Cowboys' season-opening 27–26 victory over the New York Giants.

[148] He continued to show success in the next game against the Philadelphia Eagles, but suffered a broken left collarbone during the third quarter of the 20–10 road victory after being sacked by linebacker Jordan Hicks.

[149][150] The injury sidelined Romo for eight weeks,[151] during which the Cowboys failed to win a single game with Brandon Weeden and then Matt Cassel as starting quarterback.

[155] Romo remained on the active roster until December 21 when he was placed on injured reserve after the Cowboys dropped to 4–10, officially ending their playoff hopes.

[156] Romo was unable to start in the 2016 regular season after suffering a compression fracture to the L1 vertebra in his back during the third preseason game against the Seattle Seahawks.

[157] The injury caused Romo to miss the first 10 games of the season, with the duties of the team's starting quarterback being assumed by rookie Dak Prescott.

[174][175] While there was no controversy of Romo deciding to retire and move on to broadcasting, some critics questioned Romo being immediately hired for the number one position ahead of broadcasting veterans Dan Fouts, Trent Green, or Rich Gannon, all of whom served in the number 2–4 positions, respectively, for CBS, with Fouts having once been the color commentator on Monday Night Football.

[177] Once the 2017 NFL season got underway, Romo received critical praise for his work as a recent ex-player, most notably for his ability to predict offensive plays and read defensive formations from the booth,[178][179] and "adding an enthusiasm that had been lacking with Simms.

[193] Multiple CBS executives met with Romo to discuss their concerns that he was not preparing adequately to call games and that his chemistry with Nantz had declined.

[199][200] In the Dallas area, Romo participated in community activities in collaboration with United Way, the Make-A-Wish Foundation, and the Society for the Prevention of Cruelty to Animals.

[17] In February 2018, it was announced that Romo had received a sponsor's exemption to play in the PGA Tour's Corales Puntacana Resort and Club Championship in Punta Cana, Dominican Republic from March 22–25.