Taken in the second round (17th overall) of the 1964 NFL Draft from Oregon, Mel Renfro joined the Dallas team with a background as a standout collegiate running back and track star. Head coach Tom Landry quickly saw how his speed and natural instincts on the field could boost the Dallas secondary, so he transitioned him into a defensive back. During an impressive 14-season career all with Dallas, Renfro proved Landry's foresight true by becoming one of the most talented and adaptable players in NFL secondary history.

Renfro demonstrated exceptional acceleration, seamless hip transitions, and superior ball-tracking instincts developed through experience on the track and in the backfield. He transitioned effortlessly from safety to cornerback during his career, effectively neutralizing deep vertical threats and compelling opposing quarterbacks to avoid his side of the field. His background as a ball-carrier enhanced his threat level following turnovers, as he reliably converted interceptions and kickoff returns into immediate scoring opportunities.

Renfro made an immediate impact during his rookie season in 1964, leading the National Football League in punt returns (29), punt return yards (418), kickoff returns (40), and kickoff return yards (1,017), while also intercepting seven passes. This outstanding debut earned him his first Pro Bowl selection and initiated an impressive streak of ten consecutive Pro Bowl appearances from 1964 to 1973. He reached his personal statistical zenith in 1969, leading the NFL with 10 interceptions for 222 return yards and one touchdown, thereby earning First-Team All-Pro honors.

Renfro dedicated the initial phase of his career to establishing himself as the premier free safety within the league; however, Tom Landry’s defensive scheme necessitated utmost adaptability. In 1970, Landry made the strategic and decisive choice to reassign Renfro to the position of cornerback to better contend with the league's swift split ends. The transition was executed flawlessly. Leveraging his exceptional speed in track recovery and meticulous boundary technique, Renfro effectively covered half the field for opposing passers. His proficiency in restricting primary targets through man-to-man coverage permitted Landry to fully activate the formidable capabilities of the "Doomsday Defense" front line.

Beyond his individual accolades, Renfro was the common denominator across the most iconic era in franchise history. He played in an astounding 21 playoff games for Dallas, appeared in four Super Bowls, and served as a steadying veteran presence as the secondary transitioned between generations. He started at cornerback in Dallas's victory over Miami in Super Bowl VI and contributed to another championship triumph in Super Bowl XII against Denver to cap off his career.

Renfro hung up his cleats following the 1977 season and played all 174 of his career games exclusively in Dallas. His 52 career interceptions remained the Dallas Cowboys' all-time franchise record for decades, while his 62 total takeaways (including 10 fumble recoveries) showcased his relentless nose for the football.

Over his career, Renfro recorded 52 interceptions, 13 fumble recoveries, and 2,246 return yards. In 1981, the franchise recognized his immense contributions by inducting him into the Dallas Cowboys Ring of Honor. His career reached the ultimate pinnacle in 1996, when he was enshrined in the Pro Football Hall of Fame.