East Carolina University began playing organized American football in 1932 and has had many players go on to play professionally after graduating from the university. The school's first-ever selection was Roger Thrift, a quarterback, who was picked by the Cleveland Browns in the 1951 NFL draft. The team's selection in the most recent draft, the 2021 NFL draft, was offensive tackle D'Ante Smith who was selected by the Cincinnati Bengals.

Every April, each National Football League (NFL) franchise seeks to add new players to its roster through a collegiate draft officially known as "the NFL Annual Player Selection Meeting" but more commonly known as the NFL Draft. Generally, the team with the worst record the previous year picks first, the next-worst team second, and so on. Teams that did not make the playoffs are ordered by their regular-season record with any remaining ties broken by strength of schedule. Playoff participants are sequenced after non-playoff teams, based on their round of elimination (wild card, division, conference, and Super Bowl). See NFL Draft Rules for further detail. Selections are made during seven different rounds.

Teams have the option of trading their picks to other teams in exchange for different picks, players, money, or a combination thereof. It is not uncommon for a team's actual draft pick to differ from their assigned draft pick, or for a team to have extra or no draft picks in any round due to these trades. Of the players selected in each draft and throughout its history, East Carolina has had 63 players picked.

The Pirates have had two first round selections in the NFL Draft; linebacker Robert Jones was picked #24 overall in the 1992 by the Dallas Cowboys,and running back Chris Johnson was also picked #24 overall in the 2008 NFL draft by the Tennessee Titans. The Pirates have had six players drafted by the New York Giants and five by the Dallas Cowboys and four by the Minnesota Vikings during the school's history. East Carolina most productive year was 1984, when the school had eight players selected in the draft.

Seven former Pirates: Zack Valentine (XIV), Earnest Byner (XXVI), Robert Jones (XXX), Guy Whimper (XLII), C.J. Wilson (Super Bowl XLV), Vonta Leach (Super Bowl XLVII), and John Jett (XXVII, XXX) have won Super Bowls with their respective teams. Five Pirates also have been elected to the Pro Bowl: Tony Collins (1983), Earnest Byner, (1990) and (1991), Jeff Blake, (1995), Rod Coleman (2005) and Chris Johnson (2008), (2009) and (2010).

B	Back	K	Kicker	NT	Nose tackle
C	Center	LB	Linebacker	FB	Fullback
DB	Defensive back	P	Punter	HB	Halfback
DE	Defensive end	QB	Quarterback	WR	Wide receiver
DT	Defensive tackle	RB	Running back	G	Guard
E	End	T	Offensive tackle	TE	Tight end

Draft				Player name	Position	NFL team	Notes	Ref
Year	Round	Pick	Overall
1951	28	12	339	Roger Thrift	QB	Browns	–
1961	5	8	64	Glenn Bass	TE	Cardinals	–
	23	–	–	Glenn Bass	TE	Chargers	–
1964	14	5	187	Tom Michel	RB	Vikings	–
	19	–	–	Tom Michel	RB	Raiders	–
1969	17	1	417	Wayne Lineberry	LB	Bills	–
1973	16	1	391	Tim Dameron	WR	Oilers	–
	17	22	438	Les Strayhorn	RB	Cowboys	–
1974	4	2	80	Carl Summerell	QB	Giants	–
	4	17	95	Carlester Crumpler Sr.	RB	Bills	–
1977	6	27	166	Reggie Pinkney	DB	Lions	–
1978	6	28	166	Harold Randolph	LB	Cowboys	–
1979	2	28	56	^Zack Valentine	LB	Steelers	–
	6	21	158	Eddie Hicks	RB	Giants	–
1980	11	11	288	Sam Harrell	RB	Vikings	–
	12	9	314	Mike Brewington	LB	Chiefs	–
1981	2	19	47	Tony Collins	RB	Patriots	Pro Bowl (1983)
1982	4	2	85	George Crump	DE	Patriots	–
	4	7	90	Tootie Robbins	T	Cardinals	–
1983	2	18	46	Jody Schulz	LB	Eagles	–
1984	2	27	55	Steve Hamilton	DE	Redskins	–
	4	27	111	Terry Long	G	Steelers	–
	5	3	115	Clint Harris	DB	Giants	–
	5	13	125	Jeff Pegues	LB	Redskins	–
	5	21	133	Hal Stephens	DE	Rams	–
	10	1	253	Norwood Vann	TE	Rams	–
	10	28	280	^Earnest Byner	RB	Browns	Pro Bowl (1990) (1991) 70 Greatest Redskins
	11	4	284	John Robertson	T	Eagles	–
1985	3	24	80	Stefon Adams	DB	Raiders	–
	8	4	200	Ricky Nichols	WR	Colts	–
1986	6	27	165	Kevin Walker	DB	Buccaneers	–
	10	3	252	Tony Baker	RB	Falcons	–
1988	8	5	198	Anthony Simpson	RB	Buccaneers	–
	10	4	253	Ellis Dillahunt	DB	Bengals	–
1990	3	14	67	Walter Wilson	WR	Chargers	–
	5	1	110	Junior Robinson	DB	Patriots	–
	7	14	179	James Singletary	LB	Colts	–
	10	27	275	Anthony Thompson	LB	Broncos	–
1991	9	3	226	Ernie Logan	DE	Falcons	–
1992	1	24	24	^Robert Jones	LB	Cowboys	Pro Bowl (1994)
	6	26	166	Jeff Blake	QB	Jets	Pro Bowl (1995)
	8	14	210	Luke Fisher	TE	Vikings	–
	9	26	250	Chris Hall	DB	Cowboys	–
	10	22	274	Dion Johnson	WR	Oilers	–
1993	6	8	148	Tom Scott	T	Bengals	–
1994	6	4	165	Bernard Carter	LB	Buccaneers	–
	7	8	202	Carlester Crumpler	TE	Seahawks	–
1996	4	16	111	Emmanuel McDaniel	DB	Panthers	–
	5	2	134	Jerris McPhail	RB	Dolphins	–
1997	5	1	131	Lamont Burns	G	Jets	–
1998	3	21	82	Larry Shannon	WR	Dolphins	–
1999	5	20	153	Rod Coleman	DE	Raiders	Pro Bowl (2005)
	6	32	231	Troy Smith	WR	Eagles	–
2002	4	10	108	David Garrard	QB	Jaguars	Pro Bowl (2009)
	7	30	241	Leonard Henry	RB	Dolphins	–
2004	7	45	246	Brian Rimpf	T	Ravens	–
2006	4	32	129	#Guy Whimper	T	Giants	–
2007	5	9	146	*Aundrae Allison	KR, WR	Vikings	–
2008	1	24	24	Chris Johnson	RB	Titans	Pro Bowl (2008), (2009), (2010)
2009	5	13	149	Davon Drew	TE	Ravens	–
2010	2	14	46	#Linval Joseph	DT	Giants	Pro Bowl (2017)
	7	14	221	Matt Dodge	P	Giants	–
	7	23	230	#C. J. Wilson	DE	Packers	–
2011	6	11	176	*Dwayne Harris	WR	Cowboys	Pro Bowl (2017)
2015	4	8	107	Justin Hardy	WR	Falcons	–
2017	2	5	37	Zay Jones	WR	Bills	–
2021	4	34	139	D'Ante Smith	OT	Bengals	–