Clayton was used sparingly in the offense as a rookie, appearing in 14 games and catching six passes for 114 yards and his first career touchdown, a tiebreaking 14 yard catch from Dan Marino in the fourth quarter. Miami eventually lost the game to the Buffalo Bills, 38-35. He also completed his only career pass that day, a 48-yard touchdown strike to fellow "Marks Brother," Mark Duper. Clayton's real value in his rookie season was as a punt return specialist. He totalled 392 yards on 41 returns, scoring a 60-yard touchdown in a week 12 37-0 victory over the Baltimore Colts. Miami finished 12-4, AFC East Division Champions. Wood-Strock-ino combined for an NFL second lowest 11 interceptions on the season.
In 1984, Clayton led the NFL with 18 touchdown receptions, earning his first Pro Bowl invitation. He was one of eight Dolphins on the team. Clayton was third in the NFL with 1,389 receiving yards on 73 catches. He eclipsed the 100-yard mark on six occasions, scoring two or more touchdowns four times. In a week 16 victory over the Dallas Cowboys, he caught four passes for 150 yards and three touchdowns. Miami finished the season with an AFC best 14-2 record. Clayton caught 15 additional passes for 262 yards and two scores through Miami's three playoff games, including Super Bowl XIX.
1985 would see Clayton again earn a Pro Bowl ticket, one of four Dolphins to make the cut. He led the Dolphins with 996 receiving yards, finishing second on the team with 70 passes caught and with four touchdowns. On two occasions, Clayton broke the 100-yard barrier. He would add four catches for 56 yards in two playoff games. Miami finished 12-4, winning the AFC East. The offense gained an NFL second best 5.6 yards per play.
In 1986, Clayton was one of six Dolphins at the postseason Pro Bowl. He and Mark Duper both broke the 1000-yard barrier, as Clayton's 1,150 yards and 10 touchdowns scored were second on the team. His 60 pass receptions ranked third on the Dolphins. During the season, he passed the 100-yard mark three times, and scored multiple touchdowns twice. In the season opener, he caught five passes for 143 yards and two scores, as the Dolphins fell to the San Diego Chargers, 50-28. The team finished the season at 8-8, missing the playoff cut.
Clayton led the Dolphins in 1987 with 776 receiving yards on a team second best 46 catches and seven touchdowns. His stats were undoubtedly affected by losing four games (one cancelled, three "replacement" player games). Miami finished at 8-7 (7-5 in non-replacement games), out of the playoff hunt. Clayton caught seven passes for 104 yards and two scores in a 28-10 week 13 victory over the Philadelphia Eagles.
In 1988, Clayton returned to the Pro Bowl (one of three Dolphins) by again leading the NFL with 14 touchdown catches. He led Miami with 86 catches and 1,129 yards. Clayton had five games in which he caught two touchdown passes, and on three occasions broke 100 yards. He caught 10 passes for 153 yards and two scores in a 44-30 loss to the New York Jets in week eight. Miami posted a dismal 6-10 record, finishing last in the AFC East.
1989 would see Clayton lead Miami in each receiving category, with 64 catches for 1,011 yards and nine touchdowns. He gained over 100 yards five times during the season. Miami finished out of the hunt at 8-8. Miami's passing game was still the most prolific in the AFC, with 4,216 yards gained through the air.
In 1990, Clayton was limited to 10 games due to injury in a week nine 17-3 loss to the Jets. He caught 32 passes for 406 yards and three touchdowns. Miami finished 12-4, earning a wildcard berth in the playoffs. Clayton caught nine more passes for 148 yards and a score as Miami squeaked by the Kansas City Chiefs, 17-16 before coming up short on the road to Buffalo, 44-34.
Clayton was one of three Dolphins invited to the Pro Bowl in 1991. He caught an NFL second-best 12 touchdowns as both he and Mark Duper caught 70 passes. Clayton gained a team second best 1,053 receiving yards as Miami finished the season 8-8. He had four games where he scored twice, on two occasions breaking the 100-yard mark.
In 1992, Clayton finished second on the Dolphins with 619 receiving yards on 44 catches, scoring three touchdowns. Miami won the AFC East with an 11-5 record. Miami's passing attack finished with an NFL second best 3,975 yards through the air.
Clayton joined the Green Bay Packers for the 1993 season, catching 32 passes for 331 yards and three scores. He retired following the season.
In 10 seasons with Miami, Clayton caught a Dolphins record 550 catches for 8,643 yards, second on Miami's all-time leaderboard. His 81 career touchdown catches rank 12th in NFL history.