Grossman was born in Bloomington, Indiana in 1980, the son of Rex Daniel Grossman II and Maureen Grossman. Under the motivation and guidance of his father, he began playing football at an early age in grade school. He originally started his football career as a running back. Despite his success running the ball, his mother asked his coach (his father) to convert him to a quarterback while he was in the sixth grade.

Grossman attended Bloomington High School South, where he played high school football for the Bloomington South Panthers. In three seasons as the Panthers’ quarterback, he threw for 7,518 yards and 97 touchdowns. He threw for 3,080 yards and forty-four touchdowns as a senior in 1998, including a game where he threw six touchdowns. His senior season reached its climax when he led the Panthers to a 35–14 victory over the Homestead High School Spartans in the Indiana Class 5A state championship game. Grossman completed seventeen of twenty-six pass attempts for 216 yards and five touchdowns, setting an Indiana record for the most touchdowns thrown in a championship game.

After redshirting his freshman year in 1999, Grossman competed for playing time with returning starter Jesse Palmer and the top high school recruit in the country Brock Berlin, in 2000. Grossman started his first game as a Florida Gator on October 7, 2000 against LSU. Grossman had gotten the opportunity to start after completing 13 of 16 pass attempts for 232 yards and two touchdowns against Mississippi State the week before in the Gators’ only SEC conference loss of the season. Grossman solidified his position as Florida’s starting quarterback during the next two games by throwing for over 500 yards, eight touchdowns and no interceptions in lopsided wins over LSU and Auburn. He led the Gators to the SEC championship and was named Most Valuable Player of the SEC Championship Game. For the season, Grossman completed 61.8 percent of his passes for 1,866 yards, 21 touchdowns, and only seven interceptions. His passer efficiency rating of 161.8 was the third best in NCAA Division I football.

In his three-season college career, Grossman threw for 9,164 yards and seventy-seven touchdowns. He earned a 146.77 passer rating, becoming the third most efficient passer in the Southeastern Conference’s history. He was twice chosen by his teammates as the Gators’ most valuable player, in 2000 and 2001. In one of a series of articles about the top 100 Gators from the first century of Florida football, The Gainesville Sun recognized Grossman as the No. 10 all-time Gator in 2006. He was inducted into the University of Florida Athletic Hall of Fame as a “Gator Great” in 2013.

Grossman passed for over 300 yards in nine consecutive games during his sophomore season in 2001. He led the nation in passing efficiency, passing completion percentage and yards per attempt. Grossman was recognized as a consensus first-team All-American, was voted the Associated Press Player of the Year, and came in second in the balloting for the 2001 Heisman Trophy in one of the closest Heisman votes in the history of the award. At the time, his 55 touchdown passes through his sophomore season were the most in NCAA history. On October 6, 2001, Grossman passed for 464 yards and five touchdowns as No. 2 Florida defeated the No. 18 LSU Tigers 44–15. In a 2006 interview with the Chicago Tribune, Grossman cited the victory as his most memorable game as a Gator. He finished second to University of Nebraska quarterback Eric Crouch in one of the closest votes in Heisman Trophy history, losing by only 62 votes. He earned accolades as a consensus first-team All-American, the AP National Player-of-the-Year, and finalist for other awards, including the Walter Camp National Player-of-the-Year Award, the Maxwell College Player-of-the-Year Award, and the Davey O’Brien National Quarterback-of-the-Year Award. He ended his sophomore season with a 56–23 victory over the Maryland Terrapins in the 2002 Orange Bowl.

As a junior team captain in 2002, Grossman led the Gators in the famed “Slingin’ in the Rain” game against the Tennessee Volunteers, in which he threw three touchdowns and 22 completions in 32 attempts en route to a 30–13 victory over the Vols. Grossman led the Gators to the 2003 Outback Bowl, where they lost to the Michigan Wolverines 38–30 despite his completing 21 of 41 passes for 323 yards and two touchdowns. After the season was over, Grossman decided to forgo his final year of college eligibility and declared for the NFL Draft.

Additionally, Grossman’s ability to elude pursuers and scramble significantly decreased after a season-ending leg injury in 2004. Although he only played three games in 2004, Grossman amassed more rushing yards than he did in sixteen games in 2006. However, he showed his potential to scramble during a game against the St. Louis Rams, after he converted a third and long with a twenty-two yard run. Though the run was the longest of Grossman’s career, it only gave him five net yards for the season at that point.

Grossman missed most of the 2005 season after breaking his ankle in a preseason game. On December 18, 2005, Grossman returned to the field, leading the Bears to a 16–3 victory over the Atlanta Falcons. In the following game against the Green Bay Packers, he completed eleven of sixteen passes for 166 yards for a touchdown and one interception in a 24–17 victory. Grossman’s victory enabled the Bears to clinch a playoff berth and the National Football Conference’s second playoff seed. In his first playoff game, Grossman struggled to anchor the Bears’ offense, completing 17 of 41 passes for 192 yards for one touchdown and an interception in a 29–21 loss against the Carolina Panthers.

During the 2006 Chicago Bears season, Grossman became the first Bears quarterback to start all sixteen games since Erik Kramer in 1995. In a season dubbed as a “roller coaster ride” by Grossman himself, the fourth-year quarterback had several productive performances, which were seemingly diluted by a handful of turnover-ridden games, especially in Week 6 against the Arizona Cardinals, where Grossman fumbled twice and threw four interceptions. While earning a passer rating of at least 100 in seven games, he earned a sub 50 rating in five games during the latter portion of the season. Grossman, who was recognized as the NFC Offensive Player of the Month in September, concluded the season’s final month with a 64.4 passer rating, including a zero rating during the season’s finale game against the Packers. Grossman’s work ethic drew criticism, when he admitted that he was not adequately prepared to play, and later claimed the game to be “meaningless.” After noticing that his words had been misinterpreted, he rationalized his statement days later. His inconsistent performance drew criticism, and calls for Smith to bench Grossman in favor of the veteran Brian Griese.

Grossman’s gunslinger attitude is illustrated in his desire to throw long passes, similar to his youth idol, Brett Favre. During the 2006 season, Grossman had an above average completion rate when throwing passes of twenty or more yards, but struggled to complete shorter passes. According to columnist Paul Attner of Sporting News, this attitude contributed to Grossman’s inconsistent play. During Week 12 of the 2006 season, Grossman threw a game-ending interception while attempting a deep pass to Rashied Davis. However, during a Divisional Round game in the 2006 playoffs, he threw a 68-yard touchdown pass to Berrian on the opening play of the Bears’ second drive. Grossman commented on his non-conservative play style in a 2017 interview stating, “Coach Spurrier instilled in me, don’t check down if the big play’s there. So that’s kind of how I was born. I always wanted to shoot a three-pointer in basketball, hit a home run in baseball. I don’t know why, that’s just, like, who I am.”

The following is a list of Grossman’s statistics from his regular and postseason games. Grossman has occasionally recorded notable statistics; among all quarterbacks during the 2006 season, Grossman ranked tenth in number of pass attempts, seventh in touchdowns thrown, and third in interceptions. He completed his first full season with a 73.9 quarterback rating. This was better than quarterback ratings of Favre, Peyton Manning, and Terry Bradshaw during their first full seasons; many other quarterbacks have performed similarly or better in their first years, including Grossman’s former backup Brian Griese. His twenty-three touchdowns in one season rank Grossman among the best Bears quarterbacks in franchise history. However, his twenty interceptions in one season are among the most thrown by any Bears’ quarterback in almost two decades. The unusual combination ranked Grossman as statistically the most inconsistent quarterback in almost a decade in 2006. Grossman has the NFL record for worst passer rating in a victory with at least 15 passing attempts, recording a 1.3 rating in a 23-13 Chicago Bears win over the Minnesota Vikings on December 3, 2006. In the same year, Grossman became the first quarterback to throw more interceptions than completions in a game with more than 10 passing attempts.

Before the 2007 season, Grossman vowed that he would improve his performance by simply “protecting the ball.” Smith named him as the team’s starting quarterback for the 2007 season, despite inconsistent and lackluster play throughout the preseason. Grossman struggled in his first three outings of the season, and committed ten turnovers with a 45.2 passer rating. After week three, several news sources reported that Smith demoted him in favor of Brian Griese. The official announcement came the next day, when Smith announced that Griese would start in the team’s next game. On November 11, 2007, Grossman reclaimed his first-string role after a shoulder injury sidelined Griese. Though Grossman only played for roughly one half, he led the Bears to a 17–6 victory over the Oakland Raiders with a 59-yard touchdown pass to Bernard Berrian. After reclaiming his starting role, Grossman threw three touchdowns and one interception over the course of three and a half games. He sustained a knee injury during his fifth consecutive start, and was replaced once again by Griese. Grossman was forced to relinquish his starting position to Kyle Orton, who had previously temporarily relieved him after his 2005 preseason injury.

On June 28, 2007, Grossman’s hometown of Bloomington, Indiana declared the day “Rex Grossman Day” for his accomplishments in football and the community. For the past four years, Grossman has held a charity golfing event for the Boys and Girls Club of America, raising over $100,000 for them.

Grossman became an unrestricted free agent after the 2007 season, but said he wished to return to the Bears. Bears general manager Jerry Angelo said, “We would like to have Rex back in the mix.” He added that Grossman will face additional competition if he returns, emphasizing the team’s need for a stable passing game. Smith had also voiced similar opinions. Grossman signed a new one-year contract with the Bears on February 23, 2008. Under terms of the deal, Grossman had a $3 million base salary. The Bears also granted Orton a contract extension and planned to have the two compete for a starting position. On August 18, 2008, after two preseason games, Coach Smith named Orton as the team’s starting quarterback for the 2008 season.

It was reported that Grossman absorbed a $680,000 loss on his September 2008 purchase of a 36th floor condo in the Trump International Hotel & Tower Chicago when it sold in January 2010, losing 25% of his initial investment.

Grossman became a free agent on March 1, 2009. Bears Head Coach Lovie Smith said that Grossman was not in the team’s plans for the 2009 season. During the offseason, Grossman worked out with the Cincinnati Bengals in March, but was not offered a contract. UFLaccess.com reported that Grossman would be participating in drills in a United Football League “Pro Day”. However, Grossman’s agent, Drew Rosenhaus, denied these claims, stating that “Rex will be playing in the NFL this season. We have not considered any other leagues. He will be on a NFL roster by the start of training camps.”

Grossman and his wife founded Florida Medical Staffing in 2009, a staffing agency for nurses that is based in Delray Beach, Florida.

Grossman signed a one-year contract with the Washington Redskins for the 2010 season on March 17, 2010. Grossman made his first appearance for the Redskins against the Detroit Lions on October 31, 2010, but he was sacked and lost a fumble on his first play, which was returned by Lions defensive tackle Ndamukong Suh for a touchdown. On December 17, Redskins coach Mike Shanahan benched Donovan McNabb in favor of Grossman, who had not been a starter since 2008. The Redskins fell behind the Dallas Cowboys early in the game, but Grossman threw for 322 yards, four touchdowns, and two interceptions to erase a 20-point deficit. The Cowboys still managed to win the game, 33–30. Grossman won his second start with Washington in a close and important game for the Jaguars in Jacksonville.

On August 2, 2011, Grossman re-signed with the Redskins. At the end of the 2011 pre-season, after a quarterback battle with John Beck, Grossman was chosen to be the opening day starting quarterback of the Redskins. Grossman started the 2011 season with a win against the New York Giants, completing 21 of 34 attempts while throwing for 305 yards and two touchdowns. Grossman would lead the Redskins to a 3–1 start before being benched in a four-interception week 5 performance against the Eagles in favor of Beck. Grossman returned week 10 in a loss to the Dolphins. He led a last-minute touchdown drive the next week to tie Dallas but lost in overtime. He helped the Redskins snap a six-game skid the next week with a 23–17 win over the Seattle Seahawks in which he threw 314 yards, two interceptions, and two touchdowns.

The Redskins re-signed Grossman to another one-year contract on March 17, 2012. The Redskins drafted Robert Griffin III (second overall) and Kirk Cousins (102nd overall) in the 2012 NFL Draft. Grossman became the team’s third-string quarterback and did not play in a single game for the team in 2012.

On April 3, 2013, Grossman signed another one-year contract to stay with the Redskins for 2013. He remained the team’s third-string quarterback and primarily served to advise Griffin III and Cousins.

The Cleveland Browns signed Grossman on August 12, 2014 and cut him on August 31. On December 22, the Browns offered Grossman a one-week $53,529 NFL veteran league minimum contract after losing Johnny Manziel and Brian Hoyer to injuries. Grossman passed on the offer in order to spend the holidays in Palm Beach with his family.

On August 26, 2015, Grossman signed a one-year contract with the Atlanta Falcons. The Falcons released him on September 4.