He played college football at Boise State University and was selected by the Dolphins in the fifth round of the 2015 NFL draft.

Ajayi was born in London, England, on 15 June 1993, to Nigerian parents and moved to Maryland in the United States when he was seven years old in 2000.

In October 2011, he was arrested for shoplifting after stealing a pair of sweatpants at a local Walmart and was later sentenced to five days in jail.

[17][18] Ajayi finished his final season at Boise State having accounted for 41.3% of the team's total yards and touchdowns, third among running back prospects entering the 2015 NFL draft, trailing only Melvin Gordon and Indiana's Tevin Coleman.

[19] He was named a first-team All-Mountain West Conference selection for the second consecutive season and earned third-team All-American honors by the Associated Press.

Ajayi was selected in the fifth round of the 2015 NFL draft with the 149th overall pick by the Miami Dolphins (traded from the Minnesota Vikings in exchange for Mike Wallace).

[24] On 6 September 2015, Ajayi was placed on injured reserve/designated to return due to broken ribs he suffered in the Dolphins' last exhibition game.

[27][28] After the Dolphins lost starting running back Lamar Miller to the Houston Texans via free agency, Ajayi was appointed the de facto starter going into the season.

[29] However, he was declared the backup after free agent running back Arian Foster supplanted him as the starter during training camp.

He was activated the following week and had five carries for 14 yards against the New England Patriots after Foster was sidelined in the second half due to a groin injury.

[30] After Foster's injury and eventual in-season retirement, Ajayi settled into a role as the Dolphins' lead running back.

Ajayi followed up a Week 6 204-yard and two touchdown performance against the Pittsburgh Steelers with a 214-yard and one touchdown effort against AFC East the rival Buffalo Bills in Week 7, becoming only the fourth player in NFL history along with O. J. Simpson (twice), Earl Campbell, and former Miami Dolphin Ricky Williams to rush for over two hundred yards in two consecutive games.

[35][36] In Week 16, on Christmas Eve, Ajayi recorded a third 200-yard game, again at the expense of the Buffalo Bills, including a 57-yard rush to set Andrew Franks up to kick a game-winning field goal in overtime.

In week 11 Ajayi rushed for 91 yards on 7 carries against the Dallas Cowboys, helping his team increase their record to 9–1.

That same evening, he was made the Eagles' honorary captain for the team's final regular season game against the Cowboys.