In track, Griffin broke state records for the 110-meter and 300-meter hurdles. He ran the 110-meter hurdles in 13.55 seconds and the 300-meter hurdles in 35.33 seconds. The 300 hurdles time was 1/100th of a second short of tying the national high school record at the time. He was also a gold medalist in the 110- and 400-meter hurdles on the AAU track and field circuit. In 2007, as a junior, he was rated the No. 1 high school 400-meter intermediate hurdler in the country, and was tied at No. 1 for the 110-meter sprint hurdler in the nation. His personal best in the 110-meter hurdles, 13.46 sec, ranked fifth in the world among junior athletes in 2007 (behind Noga, Brathwaite, Dutch, and Vladimir Zhukov), while his best 2007 time in the 400-meter hurdles, 49.56 sec—his personal best until 2008—led all juniors worldwide for that year. Also as a junior, Griffin received the Gatorade Texas Boys Track and Field Athlete of the Year award, and was named to USA Today′s 2007 All-USA Track and Field team. His personal best in the 400-meter hurdles was achieved on May 18, 2008, with a time of 49.22 seconds.
Coming into the 2011 season, the Baylor Bears were not expected to do well, being picked 6th in the Big 12 preseason poll. The Bears opened the season against 15th-ranked TCU. The Bears took a 47–23 lead into the 4th quarter, and were able to fight off a comeback after the Horned Frogs gained the lead 48–47 briefly, only for Baylor to kick the game-winning field goal and win 50–48. They pulled off the upset in large part due to Griffin's performance; he passed for 359 yards, with 5 touchdowns and a 77.8% completion percentage. On the game-winning drive, Griffin also caught a key pass. Following the win, Baylor entered the AP Poll rankings for only the third time in the previous 15 seasons, at 20th, and Griffin was considered by many to be a Heisman Trophy candidate. After a bye week, Baylor shut out Stephen F. Austin State University 48–0, and Griffin went 20 of 22 (90.9%) for 247 yards and 3 touchdowns and ran for 78 yards. In week 4, Griffin ushered Baylor to their third win, beating Rice University 56–31; Griffin completed 29 of 33 passes (87.9%) for 338 yards with 51 yards rushing and a touchdown. In week five against Kansas State, Griffin almost brought the Bears to their fourth win, going 23 out of 31 (74.2%) for 346 yards and 5 touchdowns with only 1 interception, but they lost 36–35 to the Wildcats. In week six against Iowa State, Griffin took Baylor to Iowa for their fourth win, completing 22 out of 30 (73.3%) for 212 yards, 1 touchdown, and no interceptions. He won the Heisman Trophy, becoming the first player from Baylor to win it. Griffin also led Baylor to a 10–3 record, including a 67–56 win over the Washington Huskies in the Alamo Bowl. With a combined 123 points, it stands as the highest-scoring regulation bowl game in NCAA history. Due to the Alamo Bowl, Griffin became the first player since Tim Tebow in 2007 to win the Heisman and not appear in the National Championship (#1 LSU faced #2 Alabama). Overall, he finished the 2011 season with 4,293 passing yards, 37 passing touchdowns, and six interceptions to go along with 179 rushes for 699 rushing yards and ten rushing touchdowns.