[10] Head coach Joe Philbin named McCain the fourth cornerback on the depth chart to begin the regular season, behind Brent Grimes, Taylor, and Davis.

[16] McCain entered training camp as the first-team nickelback, but saw competition for his role from Jordan Lucas and Tyler Patmon.

[17] Head coach Adam Gase named McCain the third cornerback on the Dolphins' depth chart to begin the regular season, behind Byron Maxwell and rookie Xavien Howard.

[18] On September 29, 2016, McCain recorded four combined tackles, deflected a pass, and made his first career sack on Andy Dalton during a 22–7 loss at the Cincinnati Bengals.

[19] On November 6, 2016, McCain recorded three solo tackles, broke up a pass, and made his first career interception in the Dolphins' 27–23 win against the New York Jets in Week 9.

McCain intercepted a pass by New York Jets' quarterback Ryan Fitzpatrick, that was originally intended for tight end Austin Seferian-Jenkins, and returned it for a 17-yard gain in the third quarter.

[21] He finished the 2016 NFL season with 45 combined tackles (32 solo), six pass deflections, one interception, one sack, and a forced fumble in 16 games and eight starts.

[24] During training camp, McCain competed to retain his position at nickelback against Tony Lippett, Michael Thomas, Cordrea Tankersley, Alterraun Verner, Jordan Lucas, and Lafayette Pitts.

[25] Head coach Adam Gase named McCain the first-team nickelback to start the season, behind Byron Maxwell and Xavien Howard.

[26] On November 26, 2017, during Week 12 against the New England Patriots, McCain was ejected for throwing a punch at wide receiver Danny Amendola.

Head coach Adam Gase named McCain and Xavien Howard the starting cornerbacks to begin the regular season in 2018.

[39] He recorded two interceptions against New York Giants quarterback Jake Fromm in the final game of the season and returned one of them for his first career touchdown.