Each of the first five selections of the 2018 MLB Draft were college players.
The Detroit Tigers made pitcher Casey Mize of Auburn the first overall pick. The San Francisco Giants followed by taking Georgia Tech catcher Joey Bart. The Philadelphia Phillies made third baseman Alec Bohm of Wichita State the No. 3 pick. Infielder Nick Madrigal of Oregon State was taken fourth by the Chicago White Sox. The Cincinnati Reds selected third baseman Jonathan India of Florida with the fifth pick.
Of the 74 players taken in the first two rounds, 35 were picked from the college ranks.
| Rd. | Pick | Team | Player | School | Pos. |
| 1 | 1 | Detroit Tigers | Casey Mize | Auburn | RHP |
| 1 | 2 | San Francisco Giants | Joey Bart | Georgia Tech | C |
| 1 | 3 | Philadelphia Phillies | Alec Bohm | Wichita State | 3B |
| 1 | 4 | Chicago White Sox | Nick Madrigal | Oregon State | 2B |
| 1 | 5 | Cincinnati Reds | Jonathan India | Florida | 3B |
| 1 | 9 | Oakland A’s | Kyler Murray | Oklahoma | CF |
| 1 | 10 | Pittsburgh Pirates | Travis Swaggerty | South Alabama | OF |
| 1 | 14 | Seattle Mariners | Logan Gilbert | Stetson | RHP |
| 1 | 18 | Kansas City Royals | Brady Singer | Florida | RHP |
| 1 | 20 | Minnesota Twins | Trevor Larnach | Oregon State | OF |
| 1 | 22 | Colorado Rockies | Ryan Rolison | Ole Miss | LHP |
| 1 | 24 | Chicago Cubs | Nico Hoerner | Stanford | SS |
| 1 | 28 | Houston Astros | Seth Beer | Clemson | 1B |
| 1C | 31 | Tampa Bay Rays | Shane McClanahan | South Florida | LHP |
| 1C | 33 | Kansas City Royals | Jackson Kowar | Florida | RHP |
| 1C | 34 | Kansas City Royals | Daniel Lynch | Virginia | LHP |
| CBA | 37 | Baltimore Orioles | Cadyn Grenier | Oregon State | SS |
| CBA | 39 | Arizona Diamondbacks | Jake McCarthy | Virginia | OF |
| CBA | 40 | Kansas City Royals | Kris Bubic | Stanford | LHP |
| CBA | 43 | St. Louis Cardinals | Griffin Roberts | Wake Forest | RHP |
| 2 | 45 | San Francisco Giants | Sean Hjelle | Kentucky | RHP |
| 2 | 46 | Chicago White Sox | Steele Walker | Oklahoma | OF |
| 2 | 49 | Atlanta Braves | Greyson Jenista | Wichita State | 1B |
| 2 | 50 | Oakland A’s | Jameson Hannah | Dallas Baptist | CF |
| 2 | 52 | Toronto Blue Jays | Griffin Conine | Duke | OF |
| 2 | 54 | Seattle Mariners | Josh Stowers | Louisville | CF |
| 2 | 56 | Tampa Bay Rays | Tyler Frank | Florida Atlantic | SS |
| 2 | 58 | Kansas City Royals | Jonathan Bowlan | Memphis | RHP |
| 2 | 59 | Minnesota Twins | Ryan Jeffers | UNC Wilmington | C |
| 2 | 65 | Washington Nationals | Tim Cate | Connecticut | LHP |
| 2 | 67 | Cleveland Indiana | Nick Sandlin | Southern Miss | RHP |
| 2 | 68 | Los Angeles Dodgers | Michael Grove | West Virginia | RHP |
| CBB | 70 | Oakland A’s | Jeremy Eierman | Missouri State | SS |
| CBB | 71 | Tampa Bay Rays | Tanner Dodson | California | RHP |
| CBB | 74 | San Diego Padres | Grant Little | Texas A&M | OF |