[9] McCoy made the Pro Bowl in each of his first three years in Buffalo, helping the team snap a 17-year playoff drought, and became one of a few select NFL running backs to surpass 10,000 career rushing yards.

[20] He had been invited to play in the Big 33 Football Classic and the U.S. Army All-American Bowl that year, but ultimately did not participate in those games as he was still recovering from his injury.

[29] As a freshman, McCoy was the point-man for the "Wildcat offense" which the Pittsburgh Panthers unveiled in a September 2007 game against the Michigan State Spartans.

[33] McCoy finished his freshman year ranked third in the Big East Conference and 25th in the NCAA Division I FBS (formerly I-A) in rushing yards with 1,328.

[36] In his final game of his freshman year, McCoy ran for 148 yards against rival West Virginia in the 100th Backyard Brawl to help the 28-point underdog Panthers defeat the then #2 Mountaineers.

[48] McCoy's final college football game of his career was the 2008 Sun Bowl played on New Year's Eve in El Paso, Texas.

[61] Westbrook sustained a concussion against San Diego[62] and McCoy was called on again to be the starter in a road game against the Chicago Bears on NBC Sunday Night Football.

[80] In the Wild Card Round of the playoffs, the Eagles faced the Green Bay Packers at Lincoln Financial Field in a rematch of the season opener.

McCoy won the FedEx Ground Player of the Year Award,[92] and was also voted Associated Press All-Pro First Team running back.

[102] McCoy took the field for Monday Night Football on September 9, 2013, and rushed for 184 yards on 31 carries and scored a touchdown in a victory over the Washington Redskins.

[105] In the following game, the Eagles faced former head coach Andy Reid and the Kansas City Chiefs in Week 3, on Thursday Night Football.

[115][116] McCoy rushed for 77 yards and one touchdown in the Eagles' Wild Card Round game against the 11–5 New Orleans Saints, but the team lost 26–24 after a last-second field goal.

[123] His most impressive game was in Week 13 in the 33–10 blowout against the Eagles' divisional rival, the Dallas Cowboys, where he ran 25 times for 159 yards and a touchdown.

[125][126] Wilbert Montgomery, the previous record holder (as well as second and third place Brian Westbrook and Steve Van Buren), had taken eight seasons to compile the yards he had, while McCoy only took six.

[134] In December, as the Bills prepared to face the Eagles in Philadelphia, McCoy said he would not shake Chip Kelly's hand, his former coach and the man who traded him.

[135] Although he kissed the Eagles logo on Lincoln Financial Field and hugged owner Jeffrey Lurie, he did not participate in postgame ceremonies when the Bills lost.

[148] Along with quarterback Tyrod Taylor and backup running back Mike Gillislee, McCoy helped Buffalo lead the NFL in rushing yards for the second consecutive year.

[151] Despite struggling early in the season in Rick Dennison's offense, McCoy had strong games against the Tampa Bay Buccaneers, Oakland Raiders, and the Los Angeles Chargers in Weeks 7, 8, and 11.

[152][153][154] During Week 14 against the Indianapolis Colts in blizzard-like conditions, McCoy had a career-high 32 carries for 156 yards and the game-winning touchdown in overtime, allowing the Bills to win 13–7.

[169] However, following the season's conclusion, Bills general manager Brandon Beane remained confident in McCoy, announcing intentions to keep him on the team through the end of his contract.

[175] He was ultimately made inactive for much of the postseason, playing just one snap in the Divisional Round against the Houston Texans, as the Chiefs went on to win Super Bowl LIV over the San Francisco 49ers.

[180] Overall, McCoy had a very limited role due to depth of the backfield unit, which contained Ronald Jones II, Leonard Fournette, and Ke'Shawn Vaughn.

McCoy's shiftiness allowed him to largely avoid the constant hits suffered by "power backs" who run directly into contact, prolonging his longevity in the league.

[197] Following his trade from the Eagles to the Bills, reports surfaced that McCoy was initially unwilling to leave Philadelphia for Buffalo, but gradually came to love his new city and its fans.

[198] In 2017, McCoy opined that Colin Kaepernick, known for starting the 2016 U.S. national anthem protests, "was not worth the distraction" when asked why the latter was not on an NFL roster that year.

[200][201] In May 2013, McCoy was sued for his alleged actions towards a woman using the alias "Mary Roe"[202] aboard a party bus on the New Jersey Turnpike.

[209] The post was soon deleted and McCoy denied all of the allegations made in a statement stating he had "not had any direct contact with any of the people involved in months."

In response, the Buffalo Bills issued a statement via Twitter stating, "We have spoken to LeSean McCoy and have been in contact with the National Football League.

[212] Court documents show that McCoy had been trying to evict Cordon from a house he owned in Milton, Georgia for some time and was concerned that she would falsely accuse him of domestic violence.

Cordon was robbed and assaulted at the home by a masked assailant on July 10, which coincidentally was the same day as a previously postponed court date for the eviction hearing.