Take the Holland Tunnel to Canal Street. Travel on Canal Street to Lafayette Avenue. Turn left on Lafayette and travel north to East Houston Street. Make a right onto East Houston and make a left onto Bowery. Travel north on Bowery to Second Street, turn right, and proceed past Second Avenue to Cathedral, which will be in the middle of the block on the right.

Cross over George Washington Bridge. Look for signs for Harlem River Drive South. Harlem River Drive becomes West Side Highway south. Continue south and exit at 23rd Street. Take 23rd Street to Second Avenue, turn right and continue south to Second Street. Turn left, and the Cathedral is in the middle of the block on the right.

Take the Midtown Tunnel to Manhattan. Follow signs for Second Avenue south and continue south to Second Street. Turn left, and the Cathedral is in the middle of the block on the right.