There were 41 Division I college players selected in the first two round of the 2016 MLB Draft.
Third baseman Nick Senzel of Tennessee was the first collegian taken with the second overall pick by the Cincinnati Reds.
There were players from 29 different schools selected. There were six schools with multiple players drafted. Florida led the way with five, while Louisville had four and Vanderbilt had three. California, Oklahoma and Virginia each had two.
There were 14 SEC players picked and 11 from the ACC.
| Rd. | Pick | Team | Player | School | Pos. | |
| 1 | 2 | Cincinnati Reds | Nick Senzel | Tennessee | 3B | |
| 1 | 5 | Milwaukee Brewers | Corey Ray | Louisville | OF | |
| 1 | 6 | Oakland A’s | A.J. Puk | Florida | LHP | |
| 1 | 8 | San Diego Padres | Cal Quantrill | Stanford | RHP | |
| 1 | 10 | Chicago White Sox | Zack Collins | Miami (Fla.) | C | |
| 1 | 11 | Seattle Mariners | Kyle Lewis | Mercer | OF | |
| 1 | 16 | Los Angeles Angels | Matt Thaiss | Virginia | C | |
| 1 | 19 | New York Mets | Justin Dunn | Boston College | RHP | |
| 1 | 21 | Toronto Blue Jays | TJ Zeuch | Pittsburgh | RHP | |
| 1 | 22 | Pittsburgh Pirates | Will Craig | Wake Forest | 3B | |
| 1 | 25 | San Diego Padres | Eric Lauer | Kent State | LHP | |
| 1 | 26 | Chicago White Sox | Zach Burdi | Louisville | RHP | |
| 1 | 27 | Baltimore Orioles | Cody Sedlock | Illinois | RHP | |
| 1 | 29 | Washington Nationals | Dane Dunning | Florida | RHP | |
| 1 | 31 | New York Mets | Anthony Kay | Connecticut | LHP | |
| 1 | 32 | Los Angeles Dodgers | Will Smith | Louisville | C | |
| 1 | 34 | St. Louis Cardinals | Dakota Hudson | Mississippi State | RHP | |
| 1 | 36 | Los Angeles Dodgers | Jordan Sheffield | Vanderbilt | RHP | |
| 1 | 37 | Oakland A’s | Daulton Jefferies | California | RHP | |
| 1 | 38 | Colorado Rockies | Robert Tyler | Georgia | RHP | |
| 1 | 39 | Arizona Diamondbacks | Anfernee Grier | Auburn | OF | |
| 2 | 43 | Cincinnati Reds | Chris Okey | Clemson | C | |
| 2 | 45 | Colorado Rockies | Ben Bowden | Vanderbilt | LHP | |
| 2 | 47 | Oakland A’s | Logan Shore | Florida | RHP | |
| 2 | 48 | San Diego Padres | Buddy Reed | Florida | OF | |
| 2 | 49 | Chicago White Sox | Alec Hansen | Oklahoma | RHP | |
| 2 | 51 | Boston Red Sox | C.J. Chatham | Florida Atlantic | SS | |
| 2 | 53 | Tampa Bay Rays | Ryan Boldt | Nebraska | OF | |
| 2 | 54 | Baltimore Orioles | Keegan Akin | Western Michigan | LHP | |
| 2 | 57 | Toronto Blue Jays | J.B. Woodman | Ole Miss | OF | |
| 2 | 58 | Washington Nationals | Sheldon Neuse | Oklahoma | 3B | |
| 2 | 59 | San Francisco Giants | Bryan Reynolds | Vanderbilt | OF | |
| 2 | 61 | Houston Astros | Ronnie Dawson | Ohio State | OF | |
| 2 | 62 | New York Yankees | Nick Solak | Louisville | 2B | |
| 2 | 64 | New York Mets | Peter Alonso | Florida | 1B | |
| 2 | 65 | Los Angeles Dodgers | Mitchell White | Santa Clara | RHP | |
| 2 | 67 | Kansas City Royals | AJ Puckett | Pepperdine | RHP | |
| 2 | 70 | St. Louis Cardinals | Connor Jones | Virginia | RHP | |
| 2 | 72 | Cleveland Indians | Logan Ice | Oregon State | C | |
| 2 | 76 | Atlanta Braves | Brett Cumberland | California | C | |
| 2 | 77 | Tampa Bay Rays | Jake Fraley | LSU | OF |