By Public Transportation:

From NYC, Upper Manhattan, and The Bronx: 
Connect to N or Q train to Ditmars Blvd. (last stop).
The N or Q train stops five blocks from St. John's Prep and the Q69 bus stops at the corner.
Walk away from the elevated tracks to Ditmars Blvd.
Make a left on Ditmars Blvd. Walk 5 blocks to Crescent Street. (between 26th and 24th Streets)
Make a right turn on Crescent Steet to the main entrance of the school.

Google Maps Transit can be helpful for planning your trip.

By Car:

From the Grand Central Parkway:
Take the 31st Street exit (last exit before the RFK Bridge, formerly Triboro Bridge). 
Bear right on Hoyt Avenue to 21st Street. Make a right onto 21st Street to 21st Avenue.  Make another right onto 21st Avenue to Crescent Street.  Take Crescent Street to the main entrance located at 21-21 Crescent Street. 

From the Brooklyn Queens Expressway:
Astoria Blvd West exit:
Immediately bear right onto 43rd Street. Take 43rd Street to 21st Avenue and make a left onto 21st Avenue.  Take 21st Avenue to Crescent Street and make a left onto Crescent Street.  Take Crescent Street to the main entrance located at 21-21 Crescent Street.

Additional information is available on the MTA website:  MTA Information